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.
Rescue Type:
RESCUE-Pharmaceutical
Rescue Paradigm:
Dvl1-/- 3+/- double mutant pregnant dams were i.p. injected daily from E9.5 to E14.5 with 4 mg/kg CHIR99021 (Tocris) dissolved in 4 mM DMSO in PBS. CHIR99021 is a potent and selective inhibitor of glycogen synthase kinase (GSK3 beta) that activates intracellular canonical Wnt signaling. Authors note that no adult male mice were found following this treatment, so all behavioral analysis is conducted in females.
Treatment does not improve measured phenotype (was expected to do so)
Ameliorated
Treatment provides partial correction or improvement of measured phenotype
No adverse effect
Treatment does not affect the parameter adversely
Sustained effect
Treatment has long term effect of restoration or amelioration, tested AFTER stopping administration (not applied for continuing long-term treatment) . Will be applied only where treatment has had restorative effects during administration or in the first battery of tests conducted.
No sustained effect
Treatment has no long term of restoration or amelioration detectable, after stopping administration. Will be applied only where treatment has had restorative effects during administration or in the first battery of tests conducted.
Description: No male dvl dms were obtained as adults as the males died postnatally after embryonic treatment with chir99021 for unknown reasons
Exp Paradigm: Male only
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
