A de novo frameshift variant in DVL3 was observed in an ASD proband from the Simons Simplex Collection (Dong et al., 2014). More recently, a Dvl1/Dvl3+/ mouse model was shown to display adult social and repetitive behavioral abnormalities associated with transient embryonic brain enlargement during deep layer cortical neuron formation, phenotypes which could be rescued by pharmacological activation of the canonical Wnt pathway (Belinson et al., 2016).
Molecular Function
This gene is a member of a multi-gene family which shares strong similarity with the Drosophila dishevelled gene, dsh. The Drosophila dishevelled gene encodes a cytoplasmic phosphoprotein that regulates cell proliferation.
External Links
References
Type
Title
Type of Disorder
Associated Disorders
Author, Year
Primary
De novo insertions and deletions of predominantly paternal origin are associated with autism spectrum disorder.
Model Type:
Genetic
Model Genotype:
Double mutant
Mutation:
Dvl 1 null mice were crossed with Dvl 3het mice, with the offspring further crossed with Dvl 1 null mice to obtain the double mutant: Dvl1-/- 3+/- ( homozygous for Dvl1 knockout and heterozygous for Dvl3).
Allele Type: Targeted(double knockout)
Strain of Origin: 129S6/SvEvTac
Genetic Background: 129S6
ES Cell Line: Mutant ES Cell Line: Model Source:
Model Type:
Genetic
Model Genotype:
Double mutant
Mutation:
BAT gal mice transgenic mice (on 129), a reporter strain that expresses beta-galactosidase in the presence of activated beta-catenin, were crossed with Dvl1 mutants to generate BAT-gal Dvl mutant mice to test the beta catenin expression in these mutants.
Allele Type: Targeted( double knockout); Reporter
Strain of Origin: 129S6/SvEvTac
Genetic Background: 129S6
ES Cell Line: Mutant ES Cell Line: Model Source:
Model Type:
Genetic
Model Genotype:
Double mutant
Mutation:
Dvl1-/- 3+/- double mutant pregnant dams i.p. injected with Brdu at 40 microg per gram mouse weight 60 min prior to embryo collection to identify proliferating cells.
Allele Type: Targeted(double knockout); Marker
Strain of Origin: 129S6/SvEvTac
Genetic Background: 129S6
ES Cell Line: Mutant ES Cell Line: Model Source:
Model Type:
Genetic
Model Genotype:
Heterozygous
Mutation:
A genomic fragment spanning from part of exon 2 through exon 7 was replaced with a neo cassette.
Allele Type: Targeted(knockout)
Strain of Origin: 129S6/SvEvTac
Genetic Background: 129S6
ES Cell Line: TC1
Mutant ES Cell Line: Model Source: JAX
Description: Neuronal precursors expressing markers sox2+ tbr2+ were increased compared to wt controls whereas sox2 alone were decreased indicating impaired neuronal differentiation in dvl dms, , the difference is observed transiently at e14.5
Exp Paradigm: NA
Description: There is a transient, but significant, increase in dorsoventral thickness of the cortical plate at e14.5, it is noted that the ventricular zone is not different in width even at e14.5
Exp Paradigm: NA
Description: Dvl dms have reduced enrichment for pou3f2 (brn2) binding sites on tbr2 as well as of beta catenin interaction with pou3f2 and axin2 promoters
Exp Paradigm: NA
Description: Beta-galactosidase staining is decreased in the cortical sections of dvl dm emryos indicating decrease in beta-catenin transcription
Exp Paradigm: NA
Description: Dvl3 hets have impaired neuronal differentiation indicated by a transient increase in sox2+tbr2+ neural precursors similar to other dvl mutants, transiently at e14.5
Exp Paradigm: NA
