Mice with disruption in Prickle2 display behavioral abnormalities including altered social interaction, learning abnormalities and behavioral inflexibility. Prickle2 disruption in mouse hippocampal neurons led to reductions in dendrite branching, synapse number and PSD size. Consistent with these findings, Prickle2 null neurons show decreased frequency and size of spontaneous miniature synaptic currents. These behavioral and physiological abnormalities in Prickle2 disrupted mice are consistent with ASD-like phenotypes present in other mouse models of ASDs. Distinct, heterozygous, rare, non-synonymous PRICKLE2 variants (p.E8Q and p.V153I) were identified in two ASD cases that were shared by their affected siblings and inherited paternally. Unlike wild-type PRICKLE2, the PRICKLE2 variants found in ASD patients exhibit deficits in morphological and electrophysiological assays (Sowers et al., 2013).
Molecular Function
This gene encodes a homolog of Drosophila prickle. The exact function of this gene is not known, however, studies in mice suggest that it may be involved in seizure prevention. Mutations in this gene are associated with progressive myoclonic epilepsy type 5.
External Links
References
Type
Title
Type of Disorder
Associated Disorders
Author, Year
Primary
Disruption of the non-canonical Wnt gene PRICKLE2 leads to autism-like behaviors with evidence for hippocampal synaptic dysfunction.
Model Type:
Genetic
Model Genotype:
Heterozygous
Mutation:
Gene targeting of Prickle2 in TT2 ES Cells.
Allele Type: Targeted (Deletion)
Strain of Origin: Genetic Background: C57BL/6
ES Cell Line: TT2
Mutant ES Cell Line: Model Source:
Model Type:
Genetic
Model Genotype:
Homozygous
Mutation:
Gene targeting of Prickle2 in TT2 ES Cells.
Allele Type: Targeted (Deletion)
Strain of Origin: Genetic Background: C57BL/6
ES Cell Line: TT2
Mutant ES Cell Line: Model Source:
Cued or contextual fear conditioning: memory of context2
Increased
Description: Abnormal contextual fear conditioning indicated by increased freezing during acquisition and recall
Exp Paradigm: Hippocampus-dependent contextual fear conditioning
Description: Decreased synaptic transmission indicated by reduced frequency of both mepscs and mipscs with no change in amplitude
Exp Paradigm: Whole-cell patch-clamp recordings of miniature excitatory post-synaptic currents from hippocampal slices
Description: Decreased social interaction indicated by less time spent directly interaction with unfamiliar mouse
Exp Paradigm: Three chamber social assay
Cued or contextual fear conditioning: memory of context2
Increased
Description: Abnormal contextual fear conditioning indicated by increased freezing during acquisition and recall
Exp Paradigm: Hippocampus-dependent contextual fear conditioning
