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DOMAINGENEDISORDERANIMAL MODELSReferences
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Mus musculusDrosophila melanogasterDanio rerioOthers
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HOMOZYGOUSHETEROZYGOUSCONDITIONAL KO/KD/KIGenetic background
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W R I T E R SASH1LMental retardation, autosomal dominant 52 (OMIM #617796)increased premature lethality after P7 and growth retardation. Surviving mutants have skeletal abnormalities, blepharitis, and infertility caused by developmental defects in both male and female reproductive organs--C57BL/6; DBA/2; ICR---Brinkmeier 2015; Zhu 2016
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CREBBPRubinstein-Taybi syndrome 1 (OMIM #180849)prenatal lethality

CBPKIX/KIX display impaired LTM for object recognition and contextual fear

CBPΔCH1/ΔCH1 display repetitive behaviors, hyperactivity, social interaction deficits, motor dysfunction, impaired recognition memory and abnormal synaptic plasticity		viable; skeletal and cardiac abnormalities; growth retardation; poor locomotor activity; long-term memory and synaptic plasticity deficits; strong defect in neuroadaptation

multilineage defects in hematopoietic differentiation and increased incidence of hematologic malignancies

reduced weight of white adipose tissue; increased insulin sensitivity and glucose tolerance; increased leptin sensitivity; increased serum adiponectin levels		CBP{HAT-} with two point mutations in adult forebrain neurons lead to impairment of two types of hippocampal-dependent memory

CBPΔ1 expression in postnatal forebrain neurons lead to synaptic plasticity deficits

cKO in neural progenitors at the median ganglionic eminence interfered with interneurons development and proper functioning of inhibitory circuitry		129; BALB/c; C57BL/6; C57BL/6J; B-CBA; DBA/2; SJLnej hemizygotes die at stage 9 or 10 during embryogenesis (most severe phenotype is the twisting of the embryo); defects in the eye specification and cell fate determination

KD caused altered geotaxis behavior, strong dendrite pruning defect during early metamorphosis, a courtship learning defect and altered development of the mushroom bodies

KD in Or47b neurons of group-housed males influenced courtship behavior		muscular dystrophy-like phenotype at 6 days of development after treatment with CREBBP inhibitor (C646)-Tanaka et al 1997; Oike et al 1999; Kung et al 2000; Yamauchi et al 2002; Bourtchouladze et al 2003; Alarcon et al 2004; Korzus et al 2004; Wood et al 2005; Wood et al 2006; Lopez-Atalaya et al 2011; Zheng et al 2016; Medrano-Fernandez et al 2019; Akimaru et al 1997; Kumar et al 2004; Boyles et al 2010; Kirilly et al 2011; Li et al 2018; Sethi et al 2019; Di Fede et al 2021; Fauquier et al 2018
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DNMT1Cerebellar ataxia, deafness, and narcolepsy, autosomal dominant (OMIM #604121), Neuropathy, hereditary sensory, type IE (OMIM #614116)embryonic lethality (do not survive past midgestation); growth retardation; reduction in 5-methylcytosine levels.

Some mutants, at 4 to 8 months of age, developed aggressive T cell lymphomas with a high frequency of chromosome 15 trisomy		Elimination of Dnmt1 by deletion of the oocyte-specific promoter and first exon from the Dnmt1 locus leads to homozygous animals that are normal, but most heterozygous fetuses of homozygous females die during the last third of gestation

Dnmt1 mutation into a mouse strain deficient for a mismatch repair protein, Mlh1 results in mice that are less likely to develop intestinal cancers that normally arise in the mismatch repair-deficient background. However, these same mice developed invasive T- and B-cell lymphomas earlier and at a much higher frequency than their Dnmt1 wildtype littermates		cKO at sequential stages of T-cell development: in early double-negative thymocytes lead to impaired survival of TCRalphabeta(+) cells and the generation of atypical CD8(+)TCRgammadelta(+) cells. In double-positive thymocytes lead to impaired activation-induced proliferation but differentially enhance cytokine mRNA expression by naive peripheral T cells

mice display 90% hypomethylated cortical and hippocampal cells in the dorsal forebrain from E13.5 through adulthood. Viable with a normal life span, but display severe neuronal cell death between E14.5 and 3 weeks postnatally. Mice exhibit neurobehavioral defects in learning and memory		129terSv; 129svJ; BALB/c; C57BL/6J---Li et al 1992; Howell et al 2001; Lee et al 2001; Trinh et al 2002; Gaudet et al 2003; Hutnick et al 2009
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DNMT3AAcute myeloid leukemia, somatic (OMIM #601626), Heyn-Sproul-Jackson syndrome (OMIM #618724), Tatton-Brown-Rahman syndrome (OMIM #615879) viable and normal at birth; most mutants become runted and died at about 4 weeks of age. KO of Dnmt3a2 in your mice lead to defects in long term memory-cKO females die in utero and lack methylation and allele-specific expression at all maternally imprinted loci examined
cKO males display impaired spermatogenesis and lack methylation at 2 of 3 paternally imprinted loci examined in spermatogonia
cKO in somatic hematopoietic stem cells: significant increase of the hematopoietic stem cells in the bone marrow after 18 weeks. None of the mutant developed leukemia		129SvJ; C57BL/6impaired viability. Transgenic flies display developmental defects and die in pupal stage. Tissue-specific expression of Dnmt3a in the eye lead to small or absent eyes--Lyko et al 1999; Okano et al 1999; Keneda et al 2004; Challen et al 2012; Olivera et al 2012
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DNMT3BImmunodeficiency-centromeric instability-facial anomalies syndrome 1 (OMIM #242860)not viable; multiple developmental defects, including growth impairment and rostral neural tube defects with variable severity at later stages of development; craniofacial, cardiac, and immune defects; lymphopenia and immunodeficiency, with lower numbers of total and mature B lymphocytes and lower IgA levels in the peripheral blood-cKO mice and their offspring showed no apparent phenotype129SvJ; C57BL/6---Okano et al 1999; Kenada 2004; Shah 2010
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EHMT1Kleefstra syndrome 1 (OMIM #610253)embryonic lethality at E9.5 with severe growth retardation autistic-like features; learning deficits and synaptic dysfunction; delayed postnatal development and increased expression of bone developmental genes; increased adult cell proliferation in the hippocampus and enhanced pattern separation ability; impaired cognitive abilities and hypoactive behaviorcKO in neuron: altered cognition, motivation and adaptive behavior
cKO in brown adipocytes: reduction of adaptive thermogenesis, obesity and systemic insulin resistance		C57BL/6; C57BL/6J; C57BL/6N; CBA; ICRLOF mutant: defects of peripheral dendrite development, larval locomotor behavior, non-associative learning, and courtship memory

overexpression in wing causes extra veins formation		--Tachibana et al 2005; Schaefer et al 2009; Balemans et al 2010; Balemans et al 2013; Ohno et al 2013; Balemans et al 2014; Benevento et al 2017; Iacono et al 2018; Kramer et al 2011; Kleefstra et al 2012
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EP300Rubinstein-Taybi syndrome 2 (OMIM #613684)nullizygotes die between E9.5 and E11.5 exhibiting defects in neurulation, cell proliferation, and heart development

homozygotes for point mutations in the KIX domain display multilineage defects in hematopoiesis (anemia, B-cell deficiency, thymic hypoplasia, megakaryocytosis and thrombocytosis) 		embryonic lethality; craniofacial anomalies and growth retardation-129Ola; C57BL/6-KD affects jaw, fin and heart progenitor populations and hypo-myelination in the CNS and PNS

muscular dystrophy-like phenotype at 6 days of development after p300 inhibition (C646 treament)		-Yao et al 1998; Kasper et al 2002; Viosca et al 2010; Babu et al 2018; Fauquier et al 2018
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EZH2Weaver syndrome (OMIM #277590)perinatal lethality viable and fertile with mild overgrowthcKO in bone marrow and thymus: defects in early B cell development and rearrangement of the immunoglobulin heavy chain gene
cKO in pancreatic β-cell: hypoinsulinemia and mild diabetes
cKO in anterior heart field cells: cardiac hypertrophy and fibrosis
cKO in retina: defects in proliferation and maturation of retina interneurons
cKO in chondrocytes: severe skeletal growth impairment
cKO in the mesenchymal, osteoblastic, and chondrocytic lineages: transient post-natal bone phenotype		129svJ; C57BL/6J; C57BL/6N; ICR-intestine structure not maintained and defects in larval caudal spinal cord regenerationXenopus laevis: KD led to defects in neural crest development and craniofacial cartilage formation O'Carroll et al 2001; Su et al 2003; Cheng et al 2009; Delgado-Olguin et al 2012; Huang et al 2014; Iida et al 2015; Feng et al 2016; Lui et al 2016; Camilleri et al 2018; Lui et al 2018; Dupret et al 2017; Tien et al 2015
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KAT6AArboleda-Tham syndrome (OMIM #616268)not viable; mice die around E14.5 or at birth and display defects in hematopoietic stem cells

KI mice with homozygous point mutations display shortened lifespan, low body weight, small thymus and spleen, and proliferation defects in hematopoietic progenitors

Kat6aΔ/Δ showed defects in craniofacial, skeletal, nervous system, thymic and cardiovascular development		Kat6aΔ/+ display normal complement of seven cervical vertebrae

Kat6a+/- display smaller spleens and significant reduction of B-cell progenitor		-129Sv; BALB/c; C57BL/6; C57BL/6J; CD-1; FVB-alteration of segmental identity (homeotic phenotype) and skeletogenesis-Katsumoto et al 2006; Thomas et al 2006; Perez-Campo et al 2009; Voss et al 2009; Voss et al 2012; Sheikh et al 2015; Vanyai et al 2019; Miller et al 2004; Crump et al 2006
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KAT6BSay-Barber-Biesecker-Young-Simpson or Ohdo syndrome (OMIM #603736)querkopf mice display craniofacial abnormalities, defects in central nervous system development and in adult neurogenesis; fail to thrive in the postnatal period--MPI-II---Thomas et al 2000; Merson et al 2006; Clayton-Smith et al 2011
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KMT2AWiedemann-Steiner syndrome (OMIM #605130):not viable with defects in segmental identity and in the hematopoietic stem cells and progenitor poolanemia; retarded growth; haematopoietic abnormalities and bidirectional homeotic transformations of the axial skeleton as well as sternal malformations; alteration of memory Th2 cell function; deficit in long-term memory formationcKO in postnatal forebrain and adult prefrontal cortex display increased anxiety and robust cognitive deficits, impaired working memory, severely impaired synaptic facilitation and temporal summation

cKO in adult ventral striatum/nucleus accumbens neurons display increased anxiety altering synaptic plasticity

cKO in adult excitatory forebrain neurons display anxiolytic behavior and impaired memory formation		C57BL/6J; C; C3H/HeJ; FVB/NJ; Ly5.2trx(Z11) hypomorphants are viable

flies displayed homeotic transformations, with a higher frequency in homozygous		severe defects in hematopoiesis; neurogenic phenotypeYu et al 1995; Yamashita et al 2006; McMahon et al 2007; Gupta et al 2010; Jakovcevski et al 2015; Shen et al 2016; Kerimoglu et al 2017; Katsani et al 2001; Wan et al 2011; Huang et al 2014
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KMT2BChildhood-onset dystonia 28 (OMIM #617284)KO before E11.5, leads to embryonic lethality with heart and/or circulation defects
KO after E11.5, mice were viable and males were infertile		hyperglycaemic; hyperinsulinaemic; non-alcoholic fatty liver diseasecKO in excitatory forebrain neurons leads to impaired hippocampus-dependent memory functionC57BL/6; C57BL/6J; C3H/HeHmutations in trr cause abnormal tissue growth in eye imaginal discs--Glaser et al 2009; Goldsworthy et al 2013; Kerimoglu et al 2013; Kanda et al 2013
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KMT2CKleefstra syndrome 2 (OMIM #617768)catalytically inactive MLL3Δ/Δ mice showed: partial embryonic lethality; stunted growth; lower fertility; very little white fat; unusual hyperproliferation; ureter epithelial tumors; hydronephrosis and kidney abnormalities--C57BL/6NKD in mushroom bodies causes defects in short-term memory

trr catalytic mutant alleles cause subtle developmental phenotypes when subjected to temperature stress or altered cohesin levels		--Lee et al 2009; Koemans et al 2017; Rickels et al 2017
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KMT2DKabuki syndrome 1 (OMIM #147920):embryonic failure before E11.5 caused by slowed growth, increased apoptosis and retarded development

recessive mutant bapa (missense mutation) showed psychomotor and behavior impairments, such as hypotonia, fine motor coordination and hyperactivity		-cKO in white pre-adipocytes inhibited adipogenesis

cKO in brown preadipocytes causes severe defects in adipogenesis and myogenesis

cKO in the dentate gyrus granule cell layer causes facial features and hippocampal memory defects		129SvEV; BALB/c; C57BL/6; C57BL/6J-mutants display skeletal defects

KD at 5 dpf display craniofacial defects and impairment in heart and brain development; gastrulation movement defects, micrognathia and neurogenesis phenotypes

null mutants has defects in vasculogenesis and angiogenesis		-Glaser et al 2006; Lee et al 2013; Bjornsson et al 2014; Yamamoto et al 2019; Bogershausen et al 2015; Laarhoven et al 2015; Tsai et al 2018; Serrano et al 2019
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KMT2EKMT2E-deficiency or O'Donnell-Luria-Rodan syndrome (OMIM #618512)incomplete postnatal lethality; growth delay; male sterility

surviving mice with exon 3 disrupted show defects in development of myeloid lineages and in lymphopoiesis 		--129S6; C57BL/6viable but females are sterile with severe oogenesis impairment

upSET deletion causes lethality in both males and females, while heterozygous flies exhibited a suppressor of variegation phenotype		--Zhang et al 2009; Madan et al 2009; Heuser et al 2009; Rincon-Arano et al 2012; McElroy et al 2017
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KMT5BMental Retardation, Autosomal Dominant 51 (OMIM #617788)embryonic lethalityviable; decreased body weight and fat; vertebral anomaliescKO in skeletal muscle leads to signs of muscular dystrophy 129Sv; C57BL/6Jsuppression of position-effect variegation-Xenopus laevis: MO display impaired neural differentiationSchotta et al 2008; Koscielny et al 2013; Neguembor et al 2013; Schotta et al 2004; Nicetto et al 2013
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NSD1Sotos syndrome (OMIM #117550)-viable; fertile; significantly smaller; decreased postnatal growth; deficits in long-term memory retention and dilation of the pelvicalyceal system -129P2Ola; C57BL/6JGOF mutants: developmental delay and reduced body size at the larval stage; pupal lethality--Migdalska et al 2012; Jeong et al 2018
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PRDM12Neuropathy, hereditary sensory and autonomic, type VIII (OMIM #616488)perinatal lethality; embryonic malformations; incorrect homeostasis; reduced size of the animalviable; do not display abnormalities compared to wild-type -C57BL/6NOrtholog of hamlet.
KD increases latency of the nociceptive responses, suggesting impaired pain perception		KD inhibits the V1-specific marker En1 and affects swimming movementsXenopus laevis: Prdm12 morphants show impaired swimming movementsHael et al 2020; Bartesaghi et al 2019; Desiderio et al 2019; Thélie et al 2015; Nagy et al 2015; Zannino et al 2014
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PRDM16Dilated cardiomyopathy, left ventricular noncompaction 8 (OMIM #615373)perinatal lethality with a distended abdomen. Craniofacial skeleton defects with anterior-specific mandibular hypoplasia; cleft palate--129SvEvBrd; C57BL/6J-KD dose-dependent: bradycardia with significantly reduced cardiac output. Significant decrease in total cardiomyocyte numbers as well as in cardiomyocyte proliferation-Bjork et al 2010; Arndt et al 2013
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PRDM5*Brittle cornea syndrome 2 (OMIM #614170)---129SvEvBrd; C57BL/6J----
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SETD2Luscan-Lumish syndrome (OMIM #616831)vascular defects in embryos and growth retardation from E8.5. Underdeveloped head and branchial arches and developmental defects (forebrain hypoplasia and unclosed neural tubes)viable-129Sv; C57BL/6-KO has small body size due to insufficient energy metabolism and protein synthesis-Liu et al 2020; Hu 2009
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SETD5Mental Retardation, Autosomal Dominant 23 (OMIM #615761)not viable; neural tube defects; heart and vascular abnormalities; developmental delayviable; embryonic developmental defects impacting early brain development; impaired social and cognitive behaviors-C57BL/6; C57BL/6J; CD-1KD affects the fish larvae morphology causing small head, cardiac edemas, and impaired neuronal migrationOsipovich et al 2016; Deliu et al 2018; Moore et al 2019; Sessa et al 2019
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WHSC1Wolf-Hirschhorn syndrome (OMIM #194190)-growth retardation; susceptible to seizures; craniofacial defects and midline (palate closure, tail kinks); ocular defects (colobomas, corneal opacities) and cardiovascular anomalies; cerebellar hypoplasia and shortened cerebral cortex-C57BL/6; C57BL/6J---Naf et al 2001; Nimura et al 2009
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E R A S E R SHDAC4Brachydactyly-mental retardation syndrome (OMIM #600430)premature ossification of developing bones due to ectopic and early onset chondrocyte hypertrophy-overexpression of Hdac4 in proliferating chondrocytes in vivo inhibited chondrocyte hypertrophy and differentiation129; C57BL/6---Vega 2004
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HDAC6Chondrodysplasia with platyspondyly, distinctive brachydactyly, hydrocephaly, and microphthalmia (OMIM #300863)mice are more resistant to chemical carcinogen-induced skin tumor formation--129SvEv---Lee 2008
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HDAC8Cornelia de Lange syndrome 5 (OMIM #300882)runted phenotype with hypoplastic, dysmorphic skulls--C57BL/6; C3H; ICR---Haberland 2009
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HRAlopecia universalis (OMIM #203655); Atrichia with papular lesions (OMIM #209500); Hypotrichosis 4 (OMIM #146550)wrinkled skin, long curved nails, and progressive irreversible hair loss within a month of birth

ENU mutants display complete baldness and hair follicles become cyst-like structures by P21		ENU mutants display sparse and short hair; hair follicles undergo normal cycling and appear to be normal, although smaller than wildtype-BALB/c; C57BL/6---Nam et al 2006; Baek et al 2009
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KDM1ACleft palate, psychomotor retardation, and distinctive facial features (OMIM #616728)--cKO myeloid-specific promoted macrophage M2 program by reprograming metabolic homeostasis through enhancing fatty acid uptake and lipolysis.

Mice were highly protected from high-fat diet-induced obesity, insulin resistance, and hepatic steatosis, and featured by the reduced accumulation of adipose tissue macrophages and repressed chronic inflammation following high-fat diet challenge		C57BL/6---Chen et al 2020
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KDM5BMental retardation, autosomal recessive 65 (OMIM #618109)major neonatal lethality. Embryos display neural defects, disorganized cranial nerves, defects in eye development, and increased incidence of exencephaly and skeletal anomalies--C57BL/6---Albert et al 2013
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KDM5CMental retardation, X-linked, syndromic, Claes-Jensen type (OMIM #300534)null mutant are not viable-cKO (exon 11 and 12) hemizygous mice exhibit smaller body size and reduced weight with adaptive and cognitive abnormalities. Their brains exhibited abnormal dendritic arborization, spine anomalies, and altered transcriptomes129S1SvImJ; C57BL/6J---Iwase et al 2016; Dickinson et al 2016
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KDM6AKabuki Syndrome 2 (OMIM #300867)embryonic lethality; reduced somite counts; females embryos display growth retardation, severe cardiac malformation and neural tube closure defects; while males display severe developmental retardation; adult females may develop myelodysplasia females are viable and fertile; males are viable at late embryonic timepoints, while at birth re small and exhibit failure to thrive phenotype (25% reached adulthood and are fertile)cKO in adult skeletal muscle stem cells display impaired muscle regeneration (not present in heterozygous female)

cKO females display neural crest induced severe craniofacial, cardiac and growth abnormalities; cKO males display moderate phenotype with mild craniofacial features and postnatal growth retardation 		129SvJ; C57BL/6; FVB/N; SWR/Jsemilethal, displaying Trithorax-like phenotypelethal at later stages of development with impairment of primordial germ cells migration

craniofacial phenotype, milder morphological defects in cardiac development and defective neuronal differentiation		-Lee et al 2012; Shpargel et al 2012; Welstead et al 2012; Thieme et al 2013; Faralli et al 2016; Shpargel et al 2017; Herz et al 2010; Van Laarhoven et al 2015
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KDM6BNeurodevelopmental disorder with coarse facies and mild distal skeletal abnormalities (OMIM #618505)------Trachemys scripta elegans (red-eared slider turtle): KO at 26 degrees Celsius (a temperature at which all offspring develop into males) triggers male-to-female sex reversal in greater than 80% of surviving embryos. Additionally, overexpression of Dmrt1 is sufficient to rescue the sex reversal induced by disruption of Kdm6bGe et al 2018
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PHF8Mental retardation syndrome, X-linked, Siderius type (OMIM #300263)--cKO display impaired learning and memory, and impaired hippocampal long-term potentiation without gross morphological defects. mTOR signaling pathway is hyperactive in hippocampus129SvJae; 129S6SvEv; C57BL/6; C57BL/6J; SWR/J---Chen et al 2018; Walsh et al 2017
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R E A D E R SAIREAutoimmune Polyendocrine syndrome type I (OMIM #240300) normal development but autoimmune features consisting in multiorgan lymphocytic infiltration, circulating auto-antibodies, infertility, altered TCR-V-beta repertoire in peripheral T cells, defects in thymic T-cell tolerance, almost complete failure to delete the organ-specific cells in the thymus, autoimmune eye disease, development of interstitial lung disease. Females dispalys oophoritis and age-dependent depletion of follicular reserves-KI mice expressing G228W mutation develop an autosomal dominant autoimmunity with reduced promiscuous gene expression of tissue-restricted antigens129Sv; C57BL/6; BALB/c; NOD--Rattus norvegicus: Aire-deficient dispaly alopecia, skin depigmentation, nail dystrophy, severe autoimmune lesions in a large spectrum of organs, in particular in the pancreas, and several autoantibodies in organs and cytokinesRamsey et al 2002; Anderson et al 2002; Liston et al 2003; DeVoss et al 2006; Gray et al 2007; Su et al 2008; DeVoss et al 2008; Shum et al 2009; Warren et al 2019; Zhang et al 2019; Ossart et al 2018
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ALG13Early Infantile Epileptic Encephalopathy-36 (OMIM #300884)increased epileptic susceptibility and severity; exacerbated reactive astrogliosis; neuronal loss; increased synaptic plasticity and affected the intracellular signaling pathway; mTOR hyperactivation--C57BL/6J---Gao et al 2019
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ASXL1Bohring-Opitz (BOPS, OMIM #605039)partially penetrant perinatal lethality, developmental phenotypes consistent with Enhancer of thritorax and Polycomb function and severe hematological phenotypes

embryonic lethal with microphthalmia/anophthalmia and dwarfism, frequent cleft palates, multiple skeletal abnormalities and myelodysplastic syndrome		viable with craniofacial dysmorphisms and mild MDS-like diseasecKO in the bone marrow niche led to a decrease in long-term-hematopoietic stem cells and myeloid lineage skewing


KI with most frequent mutations caused lead to post-natal death and possible leukemogenic events		129Sv; C57BL/6; C57BL/6Jmutations cause segmentation and homeotic phenotypes; relative mild posterior transformations and partial failure of head involution

asxl1+/− fish develop normally but appear abnormal by 7dpf and die prematurely at 14 dpf;

surviving fish are fertile but with abnormal hematopoietic system infact, they develop myeloproliferative neoplasms by 5 months		-FIsher et al 2010; Abdel-Wahab et al 2013; Wang et al 2014; Hsu et al 2017; Zhang et al 2018; Jurgens et al 1985; Sinclair et al 1992; Soto et al 1995; Sinclair et al 1998; Gjini et al 2019
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ASXL2Shashi-Pena syndrome (OMIM #617190)partially embryonic lethal, surviving mice are smaller, has shortened life span, display posterior and anterior transformations in the axial skeleton, has impaired heart function, and impaired glucose and adipocyte homeostasis. Mice develop myelodysplastic syndrome-like disease and progressive hematopoietic defects-cKO in postnatal tissues and noncompetitive bone marrow transplantation lead to leukopenia and thrombocytopenia, features of myelodysplasia and altered hematopoiesis, promoting AML1-ETO leukemogenesis129S2; C57BL/6; C57BL/6J---Baskind et al 2009; Izawa et al 2015; Li et al 2017; Micol et al 2017; Madan et al 2018
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ASXL3*Bainbridge-Ropers syndrome (OMIM #615485)-------
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BPTFNeurodevelopmental disorder with dysmorphic facies and distal limb anomalies (OMIM #617755)embryonic lethal, development arrests at the early gastrula stage (E6.5). Embryos implant but failed to establish a functional distal visceral endoderm, they manifested growth defects at the post-implantation stage and are reabsorbed by E8.5-KD inhibits cancer growth in xenograft models

inactivation in pre-neoplastic pancreatic acinar cells delays tumor development and extended survival		BALB/c; C57BL/6; CD-1; CD-45.2mutation of one copy of nurf301 enhances bithorax phenotypes (homeotic transformation), impaired heat-shock transcription factor binding and causes neoplastic transformation of larval blood cells

lacking full-length NURF leds to a spermatocyte arrest phenotype 		LOF causes abnormal craniofacial patterning-Goller et al 2008; Landry et al 2008; Dai et al 2015; Richart et al 2016; Xu et al 2018; Zhao et al 2019; Badenhorst et al 2002; Kwon et al 2009; Stankiewicz et al 2017
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BRPF1Intellectual developmental disorder with dysmorphic facies and ptosis (OMIM #617333)lethal around E9.5 with vascular defects in the placenta, yolk sac and embryo, and abnormal neural tube closurereduced dendritic complexity in both hippocampal granule cells and cortical pyramidal neurons, reduced spine density and altered spine and synapse morphologycKO in forebrain led to partial prenatal lethality; normal mice at birth, but by day 10 they are smaller; surviving mice has decreased appetite, behavioral and neurologic defects, reduced brain size, altered neocortical development, neuron progenitor production defects and corpus callosum hypoplasia

cKO in blood cells resulted in early lethality due to acute bone marrow failure and aplastic anemia		C57BL/6; C57BL/6J; C57BL/6N; ICR-anterior transformations of pharyngeal archesOryzias latipes (Medaka fish): altered patterning for skeletal developmentYou et al 2014; You et al 2015; You et al 2015; You et al 2016; Su et al 2019; Laue et al 2008; Hibiya et al 2009
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BRWD3X-linked Mental Retardation 93 (OMIM #300659)----null mutants die during larval life and have morphological defects in the developing retina; deficits in development of photoreceptors and in dendritic morphogenesis--D'Costa et al 2006; Chen et al 2015
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CBX246 XY Sex reversal 5 (OMIM #613080)more than half mutant mice die before weaning, survivors show male-to-female sex reversal and retarded formation of genital ridges

mice are sterile, 50%–75% KO Sry-positive mice are phenotypically perfect females

homeotic transformations of the axial skeleton, growth retardation, defects in gonadal, adrenal, and splenic development;

Cbx2cterm/cterm mice exhibit deficits in skeletal development and bone formation		-overexpression in hematopoietic stem and progenitor cells showed only B-cell reconstitution and these hematopoietic stem and progenitor cells failed to contribute to long-term haematopoietic reconstitution

XY KO mice developed ovaries but not testes and the gonads were hypoplastic in both sexes		129; BALB/c; C57BL/6; C57BL/6J; C57BL/6N; CD-45.1; CD-45.2---Katoh-Fukui et al 1998; Biason-Lauber et al 2009; Baumann and De La Fuente et al 2011; Katoh-Fukui et al 2012; Klauke et al 2013; Katoh-Fukui et al 2019
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DPF2*Coffin-Siris syndrome 7 (CSS7, OMIM #618027)-------
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EEDCohen-Gibson syndrome (OMIM #617561)eed-hypomorph mice survive to adults and show anterior to posterior transformation, expression of homeotic genes is unstable

eed-null mutants manifest dinstinct early gastrulation defect

mice eedI363M/I363M die at midgestation		mice eed+/I363M show perturbed hematopoietic homeostasis and increased predisposition to hematologic malignancies

mice are susceptible to malignant transformation and develop leukemia		cKO in hematopoietic cells lead to mice death in a short period with rapid decrease of hematopoietic cells and HSPCs with impaired bone marrow repopulation ability, and induced hematopoietic dysplasia

cKO in the postnatal heart cause lethal dilated cardiomyopathy

maternal cKO embryos display imprinting impairment, resulting in male-biased lethality

cKO in β-cell triggers diabetes and hyperglicemia
cKO in Schwann cells causes slow axonal regeneration
cKO in growing oocytes results in a significant overgrowth phenotype
cKO in nephron progenitor cells lead to smaller resultant kidneys showing premature loss of progenitor cells
cKO in neural stem/progenitor cells results in postnatal lethality, impaired neuronal differentiation and malformation of the dentate gyrus		129; BALB/c; C57BL/6; C57BL/6J; FWK---Schumacher et al 1996; Wang et al 2002; Ikeda et al 2016; Ueda et al 2016; Ai et al 2017; Inoue et al 2018; Lu et al 2018; Ma et al 2018; Prokopuk et al 2018; Zhang et al 2018; Liu et al 2019
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LBRPelger-Huet anomaly (OMIM #169400)mica display abnormal leukocytes and coats with short fine hair; marked abnormalities in nuclear heterochromatin

LbrGT/GT mice exhibit embryonic lethality with incomplete penetrance, shortened postnatal life span, hydrocephaly, syndactyly, chromatin atypia in neutrophils and altered morphological granulocyte maturation

LbricJ/icJ displayed skin defects and increased biomarkers of ageing		--C57BL/6; C57BL/6J; CD-1-after KD viability within 24h is reduced to 70–77% and surviving 1-day-old embryos exhibit morphological alterations including reduced growth of head structures, retardation of tail growth and a bent backbone and tail Oryctolagus cuniculus (Rabbit): homozygous offspring in an extinct rabbit lineage shows severe chondrodystrophy, developmental anomalies and increased pre- and postnatal mortalityGreen et al 1975; Shultz et al 2003; Cohen et al 2008; Solovei et al 2013; Hause et al 2018; Schild-Prüfert et al 2006; Nachtsheim 1950
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MBD5Mental Retardation Autosomal Dominant (OMIM #156200)growth retardation; wasting and pre-weaning lethality; iron overload phenotype Mbd5+/GT mice display abnormal social behavior, cognitive impairment, motor and craniofacial abnormalities and deficiency in neurite outgrowthcKO in the brain resulted in growth retardation and in disturbed glucose homeostasis and hypoglycemia129/SvEvTac; C57BL/6; C57BL/6J; C57BL/6N---Du et al 2012; Camarena et al 2014; Tao et al 2014
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MECP2Rett syndrome (OMIM #312750) or MECP2 Duplication syndrome or X-linked Syndromic Mental Retardation, Lubs type (OMIM #300260)mice die between 6 and 12 weeks, display abnormal behavior at 5 weeks, overweight and exhibit signs of physical deterioration by 8 weeks of age; at late stages of the disease mutants are hypoactive and often begin to lose weight

mice with replacement of exon 3 and 4 are viable and fertile, with no initial phenotype, but both develop a stiff uncoordinated gait and reduced spontaneous movement at 3-8 weeks; most animals subsequently develop hindlimb clasping and irregular breathing, rapid weight loss and death at approximately at 54 days

overexpression of Mecp2 results in the onset of phenotypes at 10 weeks of age with enhanced motor and contextual learning and enhanced synaptic plasticity in the hippocampus; after 20 weeks mice develop seizures, hypoactivity, and spasticity, and 30% die by 1 year of age

truncated Mecp2 allele display increased anxiety-like behavior and an enhanced physiologic response to stress

Mecp2-null mice show abnormal brain cholesterol metabolism and perturbed liver lipid profiles		mutant females are normal for the first 4 months but begin to show symptoms such as weight gain, reduced activity, ataxic gait at a later age and show substantial reduction in both brain weight and neuronal cell size

female with replacement of exon 3 and 4 also show behavioral symptoms after several months

female mice Mecp2308/X carrying a truncating mutation displayed unbalanced XCI patterns

female mice show impaired pup gathering behavior and associated auditory cortical plasticity; in response to learned maternal experience they exhibit transient changes to cortical inhibitory networks typically associated with limited plasticity		cKO in brain at E12 and in postnatal CNS neurons results in a phenotype identical to that of the null mutation

KO in Sim1-expressing neurons in the hypothalamus leads to increased anxiety-like behavior, abnormal physiologic responses to stress, including increased serum cortisol, mice are aggressive, hyperphagic, and obese, indicating dysfunction of the regulation of social and feeding behaviors

expression of hypomorphic allele in the brain caused increased body weight, increased fat, and subtle paw clasping at about 6 weeks of age, defects in fine motor control and decreased social behavior

cKO in GABA-releasing neurons (Viaat-Mecp2-/y) leads to repetitive behavior and grooming, progressive motor dysfunction, motor weakness, reduced activity by 12 weeks (hypoactive by 19 weeks), impaired hippocampal learning and memory, death of one-half mice by 26 weeks after a period of marked weight loss and after developing severe respiratory dysfunction

cKO in a subset of forebrain GABAergic neurons of male mice (Dlx5/6-Mecp2-/y) leads to repetitive behavior, impaired motor coordination, increased social interaction preference, reduced acoustic startle response, enhanced pre-pulse inhibition and survival at 80 weeks		129; 129S1SvImJ; 129S6/SvEvTac; 129SvEv; BALB/c; C57BL/6; FVBincrease in neutrophil infiltration and altered expression of inflammatory cytokinesmecp2-null zebrafish are viable and fertile with behavior alterations during early development, including spontaneous and sensory-evoked motor anomalies and defective thigmotaxis; increased neutrophil infiltration and altered expression of inflammatory cytokines

null mutation or KO or KD results in defects in peripheral innervation of trigeminal sensory neurons affecting the sensory function; inhibited neuronal differentiation leading to embryonic neural defects

morphants at 28 and 72 hpf show an increase in abnormal axonal branches of caudal primary motor neurons and a decrease in motor activity

null zebrafish displayed 		Macaca fascicularis (Monkey): expressing hMECP2 in the brain exhibit autism-like behaviors, higher frequency of repetitive circular locomotion and increased stress responses, altered social behavior, cognitive functions largely normal although some show signs of stereotypic cognitive behaviors and F1 transgenic monkeys also show reduced social interactionsChen et al 2001; Guy et al 2001; Collins et al 2004; Young and Zoghbi 2004; Moretti et al 2005; McGill et al 2006; Fyffe et al 2008; Kerr et al 2008; Samaco et al 2008; Chao et al 2010; McGraw et al 2011; Buchovecky et al 2013; Krishnan et al 2017; Vonhoff et al 2012; Gupta et al 2016; Pietri et al 2013; Leong et al 2015; Gao et al 2015; Nozawa et al 2017; van der Vaart et al 2017; Liu et al 2016
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MORC2Charcot-Maire-Tooth disease type 2Z (OMIM #616688)meiotic arrest and sterility in both sexes: spermatocytes and oocytes exhibited failures in chromosomal synapsis, blockades in meiotic recombination, and increased apoptosis -overexpression of MORC2 in a nude mouse promotes tumorigenicity and markedly enhances pulmonary metastasis of liver cancer129S4SvJae; C57BL/6---Shi et al 2018; Pan et al 2018
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MSH6Hereditary Nonpolyposis Colorectal Cancer type 5 (OMIM #614350)reduced life span, development of a spectrum of tumors (gastrointestinal tumors and B- and T-cell lymphomas), cancer susceptibility--129Ola; C57BL/6; FVBin mutants heteroduplex DNA often are unrepaired during meiotic recombination and is frequently discontinuous

homozygous flies are not capable of suppressing recombination		KO led to microsatellite instability and increased risk of tumor development (neurofibromas/malignant peripheral nerve sheath tumors, in the eye and abdomen, primitive neuroectodermal tumor in the brain and hemangiosarcoma on the head) -Edelmann et al 1997; de Wind et al 1999; Li et al 2004; Martomo et al 2004; Peled et al 2010; Feitsma et al 2008
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ORC1Meier-Gorlin syndrome 1 (OMIM #224690)lethal-cKO in embryo fibroblasts and fetal and adult diploid tissues block DNA replication, cell lineage expansion and organ development

cKO in extra-embryonic trophoblasts and hepatocytes fail to impede genome endoreduplication, organ development and function 		129; C57BL/6; C57BL/6N; FVBmutants display proliferation defects in brains and imaginal discs, abolished amplification in ovarian follicle cells, decreased cell number in salivary glands

some mutant females are sterile		KO leads to reduced body size, impaired replication licensing, slow cell cycle progression, growth retardation (primordial dwarfism); defects arising from impaired cilia function such as formation of oedema, kidney cysts, curved bodies and left-right asymmetry defects -Dickinson et al 2016; Okano-Uchida et al 2018; Park and Asano 2008; Park and Asano 2012; Bicknell et al 2011; Kuo et al 2012; Maerz et al 2019
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PHF6Borjeson-Forssmann-Lehmann syndrome (OMIM #301900)lethal

Phf6C99F/C99F mutation display deficits in cognitive functions, emotionality, and social behavior, reduced threshold to seizures and increased intrinsic excitability of entorhinal cortical stellate neurons		-cKD in the mouse cerebral cortex impair neuronal migration leading to the formation of white matter heterotopias displaying neuronal hyperexcitability

cKO in hematopoietic stem cells led to reduced numbers of CD4+ and CD8+ T cells in the peripheral blood, decreased granulocyte-monocytic progenitors, enhanced reconstitution and self-renewal capacity of HSCs, aged mice with myelodysplasia-like presentations

cKO in AgRP neurons decrease hunger-driven feeding motivation and make the mice resistant to body weight gain 		C57BL/6; C57BL/6J; C57BL/6N; CD-1; CD-45.2---Zhang et al 2013; Dickinson et al 2016; Cheng et al 2018; Hsu et al 2019; Miyagi et al 2019; Gan et al 2020
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PHIP*Developmental Delay Intellectual Disability Obesity and Dysmorphism or Chung-Jansen syndrome (OMIM #617991)--------
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RAG2Omenn syndrome and Severe Combined Immunodeficiency (OMIM #603554, #601457)mice are viable, but fail to produce mature B or T lymphocytes, total inability to initiate V(D)J rearrangement, leading to a severe combined immunodeficiency phenotype; they are more susceptible to chemically induced tumor formation, and spontaneous malignant tumors occurred late in half of mice; hypoactive immune system affected body weight and fatigue; attenuated fear responses

Rag2R229Q/R229Q mutation leads to an impaired immune tolerance and defective immune regulation



Rag2C478Y/C478Y mutation has decreased V(D)J recombination efficiency and serious impairment in T/B-cell development 		--129SvEv; C57BL/6; C57BL/10; MF1;-homozygous rag2E450fs mutant are viable and fertile, 90- and 5-day-old mutants have a striking reduction in thymic T cells, altered thymic architecture and reduced numbers of functional T and B cells-Shinkai et al 1992; Shankaran et al 2001; Golumbek et al 2007; Marrella et al 2007; Clark et al 2016; Xu et al 2016; Tang et al 2014
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RAI1Smith-Magenis syndrome (OMIM #182290)mice die during gastrulation and organogenesis, survivors are growth-retarded and display malformations in craniofacial and axial skeleton with more severe neurobehavioral abnormalities (hind limb clasping, overt seizures, motor impairment and context- and tone-dependant learning deficits)mice with deletion shows craniofacial anomalies, seizures, obesity (hyperphagia and impairment of satiety response), male-specific reduced fertility and males were hypoactive

mice with duplication are underweight and hyperactive with an impaired contextual fear conditioning

mice with higher expression displayed exacerbation of phenotype, including extreme growth retardation, severe neurologic deficits, increased hyperactivity; social behavioural deficits and hypersensitivity to light		pan-neural loss of Rai1 causes deficits in motor function, learning, and food intake

cKO in inhibitory neurons or subcortical glutamatergic neurons causes learning deficits,

cKO in Sim1+ or SF1+ cells leads to obesity		129SvEv; C57BL/6; C57BL/6J; CD-1mutations in cuff leds to female sterility and production of eggs with dorsal appendage defects --Walz et al 2003; Yan et al 2004; Bi et al 2005; Bi et al 2007; Yan et al 2007; Girirajan et al 2008; Burns et al 2010; Huang et al 2016; Diessler et al 2017; Rao et al 2017; Huang et al 2018; Parhad et al 2020
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RERENeurodevelopmental disorder with or without other anomalies (OMIM #616975):Rereom/om (null allele carrying a mutation in atrophin 2) embryos exhibit a variety of patterning defects at E8.0 including a specific failure in ventralization of the anterior neural plate, loss of heart looping and irregular partitioning of somites

embryonic lethality (E9.5-E11.5) from failure of cardiac looping and subsequent cardiac failure, defects in somitogenesis, fusion of the telencephalic vesicles, defects of the optic vesicles and failure of anterior neural tube closure		Rereom/eyes3 (null and hypomorphic allele) showed pre- and postnatal delayed cerebellum development

ventriculomegaly and incomplete closure of the optic fissure, suggestive of coloboma; reduced numbers of mesenchymal cells in their atrioventricular (AV) endocardial cushions owing to decreased levels of epithelial-to-mesenchymal transition (EMT) and mesenchymal cell proliferation		cKO in endocardium leads to hypocellularity of the atrioventricular endocardial cushions, defective EMT and ventricular septal defects129S6/SvEvTac; C57BL/6; C57BL/6J-bab mutant (in rere-a) displays disruption of posterior mesoderm formation during somitogenesis, midbrain–hindbrain boundary maintenance, and pharyngeal cartilage development Gallus gallus (white Leghorn chicken): KD in the transfected side of neural tube during early neurogenic stages causes a decreased number of dividing cells, accompanied by an increase in neurons in the developing spinal cordZoltewicz et al 2004; Kim et al 2013; Kim and Scott 2014; Fregeau et al 2016; Kim et al 2018; Plaster et al 2007; Wang et al 2017
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SMN1Spinal Muscular Atrophy (OMIM #253300, #253550, #253400, #271150)embryos display massive cell death during early embryonic development; mice SMNΔ7/Δ7 (missing exon 7) are not viable and die as embryos

Smn C-to-T mice exhibit mild adult-onset SMA characterized by muscle weakness, decreased activity and an alteration of muscle fiber size

Smn-/-; SMN2+/+ (severe SMA) mice have impaired perinatal brain development

Smn1-/-;SMN20/2TG mice (severe SMA) develop systemic inflammation in early symptomatic stages as they have an enhanced intestinal permeability, increased expression of proinflammatory cytokines and activated acute phase response in the liver		Smn+/- mice (model of type III/IV SMA) exhibit progressive loss of motor neurons, denervation of motor endplates starting at 4 weeks of age and pronounced sprouting of innervating motor axonscKO (exon 7 deletion allele) in neurons causes a severe motor deficit with tremors, reduced SMN protein in motor neuron nuclei, lack of gemini of coiled bodies and the presence of large aggregates of coilin

cKO (exon 7 deletion allele) in skeletal muscle causes muscle necrosis with a dystrophic phenotype leading to muscle paralysis and death

KD in ESCs impairs maintenance of pluripotent ESCs and neuronal differentiation		129SvEv; BALB/c; C57BL/6; C57BL/6J; FVB; MF1pupal lethality and developmental arrest in a dominant-negative manner

smn mutants (alleles containing point mutations similar to SMA patients) show abnormal motor behavior and defects at the neuromuscular junction

hypomorphic mutations cause flightlessness and acute muscular atrophy, and muscle motoneurons display pronounced axon routing and arborization defects

expressing SMA patient-derived missense mutations in larvae causes defects in developmental viability and locomotor function; in adult stage reduced longevity and locomotor defects; class III and IV fly models produced normal adults until they die between 1-7 weeks; mildest Smn missense mutations (D20V, G73R, and I93F) are phenotypically wt but by 5 weeks flies showed locomotor dysfunction and expired after 1-3 additional weeks (model moderate, later-onset Type III and IV SMA)

mutations Y203C and M194R caused the most severe phenotype phenocopying null alleles (type I SMA)

flies expressing mutations (D20V, G73R, and T205I) are also mildly affected, with G73R and D20V causing adult-onset of locomotor defects		KD induces motor axon-specific pathfinding defects and cell autonomously function

homozygous morphants for Y262X, L265X and G264D mutations are smaller, die during the second week of larval development and display a decrease in the synaptic vesicle protein

KD of three synthetic miRNA-expressing backbones reproduced SMA by targeting the smn1 gene, leading to generation of different transgenic lines with severity and age of onset recapitulating the different forms of SMA

KD with anti-smn1 miRNA expression in motor neurons reproduce SMA hallmarks, including abnormal motor neuron development, poor motor function, premature death and severe late-onset phenotypes including scoliosis-like body deformities, weight loss, muscle atrophy and motor neuron degeneration		Caenorhabditis elegans: disruption of function and overexpression result in a severe decrease in the number of progeny and in locomotive defects; its transient KD led to sterility

Caenorhabditis elegans: KD is embryonic lethal and produces a pleiotropic phenotype including late larval arrest, reduced life span, sterility, impaired locomotion and pharyngeal activity

Caenorhabditis elegans: mutant smn-1cb131 (allele resembling a point mutation in type IIIb SMA patient) swims slower and displays milder yet similar defects to null mutant 		Schrank et al 1997; Frugier et al 2000; Cifuentes-Diaz et al 2001; Le et al 2005; Kariya et al 2008; Gladman et al 2010; Murray et al 2010; Simon et al 2010; Wishart et al 2010; Chang et al 2015; Wan et al 2018; Miguel-Aliaga et al 2000; Chan et al 2003; Rajendra et al 2007; Spring et al 2019; McWhorter et al 2003; Boon et al 2009; Giacomotto et al 2015; Laird et al 2016; Miguel-Aliaga et al 1999; Briese et al 2009; Sleigh et al 2011
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SP110*Hepatic Venoocclusive disease with immunodeficiency (OMIM #235550)--------
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TAF1Mental Retardation X-Linked Syndromic 33 (OMIM #300966)--in AE (AML1-ETO fusion protein) cKI mouse bone marrow cells promoted AE driven leukemogenesis C57BL/6; C57BL/6JTAF250 null alleles are recessive larval lethal; combinations of weak LOF alleles survived to adulthood displaying defects in oogenesis, eye, ocelli, wing, bristle, development and overall growth transient KD in developing embryos induce neuronal phenotype (reduction of optic tectum area)

homozygous fishes displayed defects in embryonic development specifically in neurodevelopmental processes; heterozygous ones had no deviations		-Xu et al 2019; Wassarman et al 2000; O'Rawe et al 2015; Gudmundsson et al 2019
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TDRD7Cataract 36 (OMIM #613887)Q723X mice (nonsense mutation) develop cataracts and high intraocular pressure; in 4 weeks all null mice develop a posterior cataract that become severe with age; at later stages the lens fiber cell compartment develop vacuoles with lens capsule rupture and extrusion of fiber cell mass into the vitreous

mice develop lens opacity, diagnosed with congenital cataract, males failed to produce any pups, they have testes with significantly smaller size and lower weight and display arrested spermatogenesis at the spermiogenesis stage		--C57BL/6; C57BL/6J; C3H/JeA; DBA/2mild increase in transposon expression and decrease in piRNAs targeting transposons expressed in the germline -Gallus gallus: KD in the developing chick lens leds to cataract formation by embryonic day 16Lachke et al 2011; Tan et al 2017; Barnum et al 2020; Patil et al 2014
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ZMYND11Mental Retardation Autosomal Dominant 30 (OMIM #616083)-----bs69 mutant and bs69 overexpressing embryos display different dorsal ventral patterning defects -Sun et al 2018
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R E M O D E L E R SATRXAlpha-thalassemia myelodysplasia syndrome, somatic (OMIM #300448); Alpha-thalassemia/mental retardation syndrome (OMIM #301040); Mental retardation-hypotonic facies syndrome, X-linked (OMIM #309580)--overexpression is associated with growth retardation, neural tube defects, and a high incidence of embryonic death. Brains from E10.5 displays abnormal growth and organization of the ventricular zone that is highly convoluted in the most severely affected embryos. Transgenic mice that survive to birth exhibited a high incidence of perinatal death as well as seizures, mild craniofacial anomalies, and abnormal behavior

Forebrain-targeted cKO display widespread hypocellularity in the neocortex and hippocampus and a pronounced reduction in forebrain size. Fewer neurons reached the superficial cortical layers, despite normal progenitor cell proliferation

cKO in retina during embryogenesis resulted in loss of only 2 types of neurons, amacrine and horizontal cells		C57BL/6; C3H; FVB/N---Berube et al 2002; Berube et al 2005; Medina et al 2009
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CHD1Pilarowski-Bjornsson syndrome (617682)impaired short-
and long-term spatial memory; dysregulation of immediate early genes in the hippocampus		--C57BL/6Nwing defects including notched wing margins; male are steril e and females produced few offspring--McDaniel et al 2008; Schoberleitner et al 2019
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CHD2Epileptic encephalopathy, childhood-onset (OMIM #615369)embryonic and perinatal lethalityviable and fertile; reduced body weight; reduced body fat; postnatal runting, and growth retardation; lordokyphosis; kyphosis; normal cortical cytoarchitecture

development: reduced numbers of GABAergic interneurons, disrupted cell proliferation and neurogenesis in developing forebrain and dysregulation of genes involved in disease-related pathways, neurogenesis, and synapse organization

post-natal: disrupted excitatory and inhibitory synaptic functions in hippocampus and changes in cortical rhythmogenesis. Severe deficits in long-term spatial and recognition memory		-C57BL/6J; C57BL/6N; FVB/N-KO results in multiple developmental abnormalities: pericardial edema, microcephaly, body curvature, absent swim bladder, and stunted growth. Mutant zebrafish larvae also showed abnormal movement patterns, such as twitching and trembling-Kulkarni et al 2008; Kim et al 2018; Suls et al 2013
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CHD3Snijders Blok-Campeau syndrome (OMIM #618205)partial embryonic lethality--C57BL/6J; C57BL/6N; FVB/N---Xie et al 2020
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CHD4Sifrim-Hitz-Weiss syndrome (OMIM #617159)--cKO in granule neurons of the mouse cerebellum increases accessibility of gene regulatory sites genome-wide in vivo; promotes recruitment of the architectural protein complex cohesin preferentially to gene enhancers in granule neurons in vivo; strengthens interactions among developmentally repressed contact domains as well as genomic loops in a manner that tightly correlates with increased accessibility, enhancer activity, and cohesin occupancy at these sitesC57BL/6; DBA/2---Goodman et al 2020
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CHD7CHARGE syndrome (OMIM #214800); Hypogonadotropic hypogonadism 5 with or without anosmia (OMIM #612370)embryonic lethality after E10.5 defects with reduced penetrance; prenatal death; cleft palate; choanal atresia; septal defects of the heart; hemorrhages; genitalis defects; and keratoconjunctivitis sicca; loss of odor-evoked electroolfactogram responses; smaller olfactory bulbs; reduced olfactory sensory neurons; disorganized epithelial ultrastructure, despite apparently normal functional cilia and sustentacular cells. Significant reductions in the proliferation of neural stem cells and regeneration of olfactory sensory neurons-129S1Sv1mJ; BALB/creduced kismet (CHD7) expression lead to defects in memory and motor function--Bosman et al 2005; Layman et al 2009; Melicharek et al 2010; Bosman et al 2005
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CHD8Autism susceptibility 8 (OMIM #615032)embryonic lethalityviable and fertile; increased brain weight and volume; shorter intestine and slower intestinal transit; ASD-like behavioral feautres including increased anxiety, repetitive behavior, and altered social behavior; macrocephaly; abnormal craniofacial features; synaptic dysfunction in medium spiny neurons of the nucleus accumbens; impaired motor skills; hypertelorism; pronounced hypoactivity; anomalous responses to social stimuli and increased synchronized activity in cortico-hippocampal and auditory-parietal networks

Chd8+/del5 display cognitive impairment correlated with increased regional brain volume; increased neuronal proliferation and developmental splicing perturbation

Chd8+/N2373K display a range of abnormal behaviors during pup, juvenile, and adult stages only in males		KD in utero in layers II and III neurons at E13 displays reduced cortical neural proliferation; dendritic arborization and spine density; behavioral deficits in adult mice

KO in preadipocytes leads to impaired adipogenesis

KD in neocortex displays reduced axon and dendritic growth; disruption of axon projections to the contralateral cortex; delayed neuronal migration at E18.5 		C57BL/6; C57BL/6J; C57BL/6N; CFWkismet mutants display alterations in the development of the central region of the wing; reduced synaptic vesicle marker at stimulated but not resting synapses

kismet LOF in intestinal stem cells displays increase self-renewal in these cells		morphants display head overgrowth without gross developmental abnormalities, neuronal development and impairment of gastrointestinal motility

overexpression of truncated cdh8 form causes brain disruption phenotypes		Xenopus laevis: KD displays ectopic sonic hedgehog expressionNishiyama et al 2004; Katayama et al 2016; Durak et al 2016; Platt et al 2017; Gompers et al 2017; Jung et al 2018; Kita et al 2018; Suetterlin et al 2018; Xu et al 2018; Terriente-Felix et al 2011; Gervais et al 2019; Latcheva et al 2019; Bernier et al 2014; Sugathan et al 2014; Kunkel et al 2018
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SMARCA2Nicolaides-Baraitser syndrome-4 (OMIM #601358)viable, fertile and slightly larger than normal with impaired social interaction and prepulse inhibition--129Sv; C57BL/6; C57BL/6Jdominant-negative transgene resulted in peripheral nervous system defects, homeotic transformation and decreased viability; defects in initiation of the pruning of the nervous system (MBγ neuron) during early metamorphosis (in pupae)

KD results in generation of extra neuroblast andvdefects in maintenance of MBγ axon survival during ageing and in short- and long-term memory 		--Reyes et al 1998; Koga et al 2009; Elfring et al 1998; Neümuller et al 2011; Kirilly et al 2011; Chuback et al 2019
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SMARCA4Coffin-Siris syndrome-4 (OMIM #614609)death during periimplantation stage half litter dies before 3 weeks and neonatal mice display congenital heart defects; predisposition to exencephaly and apocrine tumorscKO in T cell develop thymic abnormalities and immunodeficiency

cKO in oocytes display zygotic genome activation defect in embryos

cKO in adult cardiomyocytes display pathological alpha to beta myosin heavy chain shift and hypertrophy

cKO in retina lead retina degeneration		129Sv; C57BL/6; C57BL/6N; Black Swiss; CD-1-young (yng) phenotype showed a defect in terminal differentiation of retinal cells

hypoplastic heart with severe arhythmias and sporadic arrest in contraction; KO by MO causes severe stenosis in heart chamber 		Xenopus laevis: reduction of brg1 expression by MO affected neuronal differentiationBultman et al 2000; Gebuhr et al 2003; Bultman et al 2006; Hang et al 2010; Takeuchi et al 2011; Aldiri et al 2015; Gregg et al 2003; Seo et al 2005
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SRCAPFloating Harbor syndrome (OMIM #136140)----dom mutation display prolonged larval development followed by lethality at pupariation; homozygous larvae were devoid of imaginal discs and histoblasts; reduced neuroblast region in the brain; melanized hematopoietic organ; no circulating hemocytes

LOF mutations lead to larval or pupal lethality; defects in hematopoiesis and wing development; female infertility		--Braun et al 1997; Ruhf et al 2001
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* In red genes with no animal model described
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