Event Title

Effect of a loss of WRC formation on autistic behavior modulation

Advisor(s)

Dr. Jennifer Rakotomamonjy; Northwestern University, Feinberg School of Medicine

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

Discipline

Biology

Start Date

21-4-2021 9:10 AM

End Date

21-4-2021 9:25 AM

Abstract

It has been determined that pathological Wave Regulatory Complex (WRC) variants can result in intellectual disability with autistic features and seizures. The WRC is a five-protein complex consisting of WAVE1, CYFIP1, ABI2, NAP1, and HSPC300. The WRC mediates interactions of membrane receptors with the actin cytoskeleton to regulate crucial developmental steps such as neural adhesion and migration. The deletion of ABI2 in mice has been found to reduce actin nucleation and produce neural phenotypes that include deficits in memory and other cognitive skills. Wave1 knockout mice showed behavioral abnormalities, including impaired learning and memory. This study was focused on the Abi2 gene, where point mutations were introduced to prevent the binding of the WRC and 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 21st, 9:10 AM Apr 21st, 9:25 AM

Effect of a loss of WRC formation on autistic behavior modulation

It has been determined that pathological Wave Regulatory Complex (WRC) variants can result in intellectual disability with autistic features and seizures. The WRC is a five-protein complex consisting of WAVE1, CYFIP1, ABI2, NAP1, and HSPC300. The WRC mediates interactions of membrane receptors with the actin cytoskeleton to regulate crucial developmental steps such as neural adhesion and migration. The deletion of ABI2 in mice has been found to reduce actin nucleation and produce neural phenotypes that include deficits in memory and other cognitive skills. Wave1 knockout mice showed behavioral abnormalities, including impaired learning and memory. This study was focused on the Abi2 gene, where point mutations were introduced to prevent the binding of the WRC and 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.