De novo loss-of-function variants in the PAX5 gene have been identified in two simplex ASD cases (Iossifov et al., 2014; O'Roak et al., 2014). A de novo likely damaging missense variant in PAX5 was identified in an ASD proband from the SPARK cohort (Feliciano et al., 2019); in the same report, a meta-analysis of de novo variants in 4773 published ASD trios and 465 SPARK trios using TADA identified PAX5 as an ASD candidate gene with a q-value 0.1.
Molecular Function
May play an important role in B-cell differentiation as well as neural development and spermatogenesis.
External Links
References
Type
Title
Type of Disorder
Associated Disorders
Author, Year
Primary
De novo gene disruptions in children on the autistic spectrum.
Homozygous Pax5 mutant mice showed postnatal lethality where mutants became growth retarded in the second week and mostly died within 3 weeks (Urbánek, 1994). However, the authors reported that 11/200 HM mice survived the first 3 weeks and continued as underdeveloped animals for up to 7 months with accommodations such as delayed weaning and access to a second, surrogate nursing female. In a second study, conditional knockout models were generated by deleting Pax5 in GABAergic neurons (Ohtsuka, 2013). About 47% of conditional homozygous mutant mice and 19% of heterozygous mice developed hydrocephalus around postnatal day 50 and died approximately one to two weeks thereafter.
References
Type
Title
Author, Year
Additional
GABAergic neurons regulate lateral ventricular development via transcription factor Pax5
Model Type:
Genetic
Model Genotype:
Homozygous
Mutation:
Cre-IRES-LacZ transgene was inserted at the first coding ATG of the Gad1 gene to achieve Cre-expression in GABAergic neurons. These mice were crossed with Pax5 floxed mice for Cre-mediated recombination of Pax5.
Allele Type: conditional knockout
Strain of Origin: CBA/C57 hybrid
Genetic Background: C57BL/6
ES Cell Line: Mutant ES Cell Line: Model Source: 11420047; 23349049
Model Type:
Genetic
Model Genotype:
Heterozygous
Mutation:
Cre-IRES-LacZ transgene was inserted at the first coding ATG of the Gad1 gene to achieve Cre-expression in GABAergic neurons. These mice were crossed with Pax5 floxed mice for Cre-mediated recombination of Pax5.
Allele Type: conditional knockout
Strain of Origin: CBA/C57 hybrid
Genetic Background: C57BL/6
ES Cell Line: Mutant ES Cell Line: Model Source: 11420047; 23349049
Model Type:
Genetic
Model Genotype:
Homozygous
Mutation:
Most of exon 2 was replaced by a lacZ/neo cassette.
Allele Type: knockout
Strain of Origin: Genetic Background: 129/Sv
ES Cell Line: D3-15, D3-16, D3-30
Mutant ES Cell Line: Model Source:
Model Type:
Genetic
Model Genotype:
Heterozygous
Mutation:
Most of exon 2 was replaced by a lacZ/neo cassette.
Allele Type: knockout
Strain of Origin: Genetic Background: 129/Sv
ES Cell Line: D3-15, D3-16, D3-30
Mutant ES Cell Line: Model Source:
Mortality/lethality: life span: incomplete penetrance1
increased
Description: Gad1-Pax5 KO mice died 1-2 weeks after appearance of macroscopic changes; animals that donâ??t develop phenotype by P60 survive 12 months or more, and are fertile
Mortality/lethality: life span: incomplete penetrance1
increased
Description: Gad1-Pax5 KO mice died 1-2 weeks after appearance of macroscopic changes; animals that donâ??t develop phenotype by P60 survive 12 months or more, and are fertile
Morphology of the superior and inferior colliculi1
abnormal
Description: dramatic reduction in the inferior colliculus in the central region, left and right of the midline, lateral sides were normal in size; superior colliculus was normal
Description: homozygous mice showed altered foliation pattern; the lobule culmen was divided by a deep intraculminate fissure and slight change in folding of the tuber vermis
Description: homozygous mutant mice were born alive and usually dies within 3 weeks, 11/200 HM mice passed critical period of 3 weeks and lived as runted animals for up to 7 months with weaning postponed and having access to a second, surrogate nursing female.
