A de novo missense variant in the DPYSL3 gene was identified in an ASD proband from the Simons Simplex Collection in Iossifov et al., 2014; this variant was predicted to be possibly damaging and was present in both dbSNP and ESP. A rare de novo missense variant in DPYSL3 (p.Ser541Tyr) that was experimentally shown to result in a partial loss-of-function effect was identified in an ASD proband from the Central Ohio Registry for Autism (CORA) in Tsutiya et al., 2017. Tsutiya et al., 2017 further demonstrated that DPSYL3 knockout mice exhibited reduced social interaction and several alterations in sensory responses, with most of these changes being more severe in male mice than in females.
Molecular Function
Necessary for signaling by class 3 semaphorins and subsequent remodeling of the cytoskeleton. Plays a role in axon guidance, neuronal growth cone collapse and cell migration
External Links
References
Type
Title
Type of Disorder
Associated Disorders
Author, Year
Primary
The contribution of de novo coding mutations to autism spectrum disorder
Dpysl3-KO mice showed decreased social interaction but no change in social dominance. Dpysl3-KO mice show normal olfaction and pain perception. Male Dpysl3 mice show difference in USV emission in response to familiar and unfamiliar bedding and differences in thermal perception. Most changes were more severe in male knockout mice than in females. The mRNA expression levels of some genes related to neurotransmission and cell adhesion were altered in the brain of Dpysl3-KO mice, mostly in a gender- and brain region-dependent manner. Dpysl3-KO mice show normal activity level, no increase in anxiety and normal novel object recognition (Tsutiya A., Sci. Rep., 2017).
References
Type
Title
Author, Year
Primary
Human CRMP4 mutation and disrupted Crmp4 expression in mice are associated with ASD characteristics and sexual dimorphism.
Model Type:
Genetic
Model Genotype:
Homozygous
Mutation:
A floxed neomycin resistance cassette replaced exon 4..
Allele Type: knockout
Strain of Origin: Genetic Background: C57BL/6N
ES Cell Line: Not specified
Mutant ES Cell Line: Not specified
Model Source: Acc. No. CDB0637K: http:// www.cdb.riken.jp/arg/mutant%20mice%20list.html) PMID# 22234963
Description: Mutant females show higher expression of glur2 mrna expression in the olfactory bulb, than in wt females. mutant males show higher expression of hippocampal glur1 mrna expression than in wt males and mutant females. mutant males show higher glur2 mrna expression than wt males.
Exp Paradigm: NA
Description: Mutant females show higher gabaa1, gabaa2, gababr1, and vgat mrna expressions than in wt females and mutant males. female mutants show higher expression of gabaa1 and gababr1 compared to mutant males. mutant females show lower gabaa2 mrna expression compared to wt females. mutant males show lower gababr1 expression than wt males.
Exp Paradigm: NA
Description: Male mutants emit more uvs at 9 c than at 19 c whereas male wildtype pups emit fewer uvs at 9 c than at 19 c. male mutants emit more usvs at 9 deg c compared to controls. male mutants emit more usvs at 9 deg c compared to female mutants.
Exp Paradigm: NA
Description: Male mutants show decrease in time spent with unfamiliar stimulus mouse compared to controls. the time spent sniffing the novel object versus the stranger mouse was not significantly different in mutant males compared to controls.
Exp Paradigm: NA
Description: Mutants show fewer number of uvs under two different smell stimuli, familiar and unfamiliar nest bedding, compared to controls. number of uvs emitted by male and female mutant pups did not differ significantly between familiar and unfamiliar bedding. number of uvs emited by male mutant pups in response to unfamiliar bedding was reduced compared to controls.
Exp Paradigm: Ultrasonic volcalization in response to familiar and unfamiliar odour.
Description: Mutants show difference in expression of glur1, glur2, vglut1, vglut2, gabaa1, gabaa2, gababr1, vgat, ncam1 and n-cadherin compared to controls, varying based on sex and brain region. mutant male and female mice show higher expression of vglut1 and ncam1 mrna in the ob than in wt mice of the same sex. mutants show lower ncam1 and n-cadherin mrna expressions than wt mice of the same sex.
Exp Paradigm: NA
