Dvl1-deficient mice have previously been shown to demonstrate abnormal social behavior (Lijam et al., 1997; Long et al., 2004). 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
DVL1, the human homolog of the Drosophila dishevelled gene (dsh), encodes a cytoplasmic phosphoprotein that regulates cell proliferation, acting as a transducer molecule for developmental processes, including segmentation and neuroblast specification. The encoded protein participates in Wnt signaling by binding to the cytoplasmic C-terminus of frizzled family members and transducing the Wnt signal to down-stream effectors. There is evidence that heterozygous mutations in DVL1 are responsible for autosomal dominant Robinow syndrome-2 (DRS2; OMIM 616331).
External Links
References
Type
Title
Type of Disorder
Associated Disorders
Author, Year
Primary
Social interaction and sensorimotor gating abnormalities in mice lacking Dvl1.
Dvl1null animals display transient anomalies in neuroanatomy during embryonic development, have normal survival rates and display social deficits as adults.
References
Type
Title
Author, Year
Primary
Prenatal -catenin/Brn2/Tbr2 transcriptional cascade regulates adult social and stereotypic behaviors.
Model Type:
Genetic
Model Genotype:
Homozygous
Mutation:
A neomycin cassette replaced part of exon 2 and exons 3 and 4 completely.
Allele Type: Targeted(knockout)
Strain of Origin: 129S6/SvEvTac
Genetic Background: 129S6
ES Cell Line: TC1
Mutant ES Cell Line: Model Source: JAX
Model Type:
Genetic
Model Genotype:
Homozygous
Mutation:
BAT gal mice transgenic mice (on 129) ,a reporter strain that express 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(knockout); Reporter
Strain of Origin: 129S6/SvEvTac
Genetic Background: 129S6*129
ES Cell Line: Mutant ES Cell Line: Model Source:
Model Type:
Genetic
Model Genotype:
Homozygous
Mutation:
Dvl1 -/- pregnant dams i.p. injected with BrdU at 40 microg per gram of mouse weight 60 min prior to embryo collection to identify proliferating cells.
Allele Type: Targeted(knockout); Marker
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:
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:
Description: Dvl1 mutants have a transient but significant increase in number of sox2+ tbr2+ neural precursor cells only at e14.5 indicating impaired neuronal differentiation
Exp Paradigm: NA
Description: Pou3f2 levels are decreased compared to wt in the frontal cortex (it is noted that tbr2 and beta-catenin levels were not changed)
Exp Paradigm: NA
Description: Beta-galactosidase staining is decreased in the cortical sections of dvl1 mutant emryos indicating decrease in beta-catenin transcription
Exp Paradigm: NA
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
