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SCSB Colloquium Series – Craig M. Powell, M.D., Ph.D.
April 3, 2019 | 4:00 pm - 5:00 pm
Wednesday, April 3, 2019
Time: 4:00 pm-5:00 pm, followed by reception
Speaker: Craig M. Powell, M.D., Ph.D.
Affiliation: Professor and Chair, Department of Neurobiology, University of Alabama at Birmingham School of Medicine
Hosts: Gloria Choi, Ph.D., Troy Littleton, Ph.D.
Talk title: Genetic Models of Autism: Molecules to Potential Therapeutics
Abstract: 16p11.2 copy number variants (CNV) are linked to neuropsychiatric disorders and are among the most prevalent CNVs in autism spectrum disorders (ASDs). Of many 16p11.2 genes, KCTD13 has been implicated as a major driver of neurodevelopmental phenotypes in zebrafish. The function of KCTD13 in mammalian brain, however, remains unknown. Here we delete Kctd13 in mice and demonstrate reduced synaptic transmission. Reduced synaptic transmission correlates with increased levels of RhoA, a KCTD13/CUL3 ubiquitin ligase substrate, and is reversed by RhoA inhibition, suggesting increased RhoA as an important mechanism. In contrast to a previous knockdown study, deletion of Kctd13 does not increase brain size or neurogenesis in mice or zebrafish. These findings implicate Kctd13 in regulation of neuronal function relevant to neuropsychiatric disorders and clarify the role of Kctd13 in neurogenesis and brain size. Our data also reveal a potential role for RhoA as a therapeutic target in disorders associated with KCTD13 deletion. Unpublished data will be presented on KCTD13 binding partner and ubiquitinating enzyme CUL3.