PRRG4 Brain-Specific Conditional Knockout Mice Display Autism Spectrum Disorder-Like Behaviors

Area of Science:

• Neuroscience
• Genetics
• Developmental Biology

Background:

• Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder with poorly understood mechanisms.
• The PRRG4 gene deletion is implicated in ASD symptoms within WAGR syndrome.
• A mouse model for PRRG4 gene deletion in the brain was previously unreported.

Purpose of the Study:

• To investigate if brain-specific conditional knockout of PRRG4 induces ASD-like symptoms in mice.
• To explore the role of PRRG4 in neural development and synaptic function.

Main Methods:

• Generation of brain-specific PRRG4 knockout mice (PRRG4-CKO) using Emx1-Cre and PRRG4fl/fl mice.
• Behavioral tests to assess social deficits, repetitive behaviors, and anxiety.
• Analysis of dendritic morphology, spine density, synaptic protein levels, and RhoA activity.

Main Results:

• PRRG4-CKO mice displayed significant social deficits, repetitive behaviors, and anxiety.
• Knockout led to increased dendritic complexity and spine density in cortical and hippocampal neurons.
• Reduced interaction between PRRG4 and MAGI2, and decreased RhoA-GTP levels were observed.

Conclusions:

• Brain-specific PRRG4 knockout induces ASD-like phenotypes in mice.
• PRRG4 protein regulates dendritic and synaptic development, potentially via MAGI2 interaction and RhoA activation.
• Findings support the link between PRRG4 loss and ASD phenotypes in WAGR syndrome.