Event Title

Effect of a loss of WRC formation on autistic behavior modulation

Session Number

Project ID: BIO 06

Advisor(s)

Dr. Jennifer Rakotomamonjy; Northwestern Feinberg School of Medicine,

Dr. Alicia D Guemez Gamboa; Northwestern Feinberg School of Medicine

Discipline

Biology

Start Date

22-4-2020 9:45 AM

End Date

22-4-2020 10:00 AM

Abstract

It has been recently described that pathogenic variants in different components of the Wave Regulatory Complex (WRC) result in intellectual disability with autistic features and seizures. The WRC is a five-protein complex consisting of WAVE1, CYFIP1, ABI2, NAP1, and HSPC300 that mediates interactions of membrane receptors with the actin cytoskeleton to regulate crucial developmental steps such as neural adhesion and migration. Deletion of ABI2 in mice reduces actin nucleation and produces phenotypes in the brain including deficits in memory and other cognitive skills. Wave1 knockout mice showed behavioral abnormalities, including impaired learning and memory. In this study, I used a mouse model where we introduced point mutations in Abi2 to prevent WRC binding to cell membrane partners. Wild-type, heterozygous and homozygous mice for the Abi2 point mutations were observed in the nestlet shredding animal model to determine if the loss of WRC formation resulted in repetitive behavior reminiscent of obsessive-compulsive disorder or autism spectrum disorders. My results show no significant differences between genotypes, suggesting that the formation of the WRC does not play a major role in autistic behavior modulation. Further investigation is needed to explore seizure susceptibility and assess behaviors related to intellectual disability in our mouse model

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Apr 22nd, 9:45 AM Apr 22nd, 10:00 AM

Effect of a loss of WRC formation on autistic behavior modulation

It has been recently described that pathogenic variants in different components of the Wave Regulatory Complex (WRC) result in intellectual disability with autistic features and seizures. The WRC is a five-protein complex consisting of WAVE1, CYFIP1, ABI2, NAP1, and HSPC300 that mediates interactions of membrane receptors with the actin cytoskeleton to regulate crucial developmental steps such as neural adhesion and migration. Deletion of ABI2 in mice reduces actin nucleation and produces phenotypes in the brain including deficits in memory and other cognitive skills. Wave1 knockout mice showed behavioral abnormalities, including impaired learning and memory. In this study, I used a mouse model where we introduced point mutations in Abi2 to prevent WRC binding to cell membrane partners. Wild-type, heterozygous and homozygous mice for the Abi2 point mutations were observed in the nestlet shredding animal model to determine if the loss of WRC formation resulted in repetitive behavior reminiscent of obsessive-compulsive disorder or autism spectrum disorders. My results show no significant differences between genotypes, suggesting that the formation of the WRC does not play a major role in autistic behavior modulation. Further investigation is needed to explore seizure susceptibility and assess behaviors related to intellectual disability in our mouse model