| Literature DB >> 29088697 |
Christine Ochoa Escamilla1, Irina Filonova1, Angela K Walker1, Zhong X Xuan1, Roopashri Holehonnur1, Felipe Espinosa1, Shunan Liu1, Summer B Thyme2, Isabel A López-García1, Dorian B Mendoza1, Noriyoshi Usui3, Jacob Ellegood4, Amelia J Eisch5, Genevieve Konopka3, Jason P Lerch4,6, Alexander F Schier2,7,8,9,10, Haley E Speed1, Craig M Powell1,3,5.
Abstract
Copy-number variants of chromosome 16 region 16p11.2 are linked to neuropsychiatric disorders and are among the most prevalent in autism spectrum disorders. Of many 16p11.2 genes, Kctd13 has been implicated as a major driver of neurodevelopmental phenotypes. The function of KCTD13 in the mammalian brain, however, remains unknown. Here we delete the Kctd13 gene in mice and demonstrate reduced synaptic transmission. Reduced synaptic transmission correlates with increased levels of Ras homolog gene family, member A (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 or kctd13 does not increase brain size or neurogenesis in mice or zebrafish, respectively. These findings implicate Kctd13 in the 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.Entities:
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Year: 2017 PMID： 29088697 PMCID： PMC5787033 DOI： 10.1038/nature24470
Source DB: PubMed Journal: Nature ISSN： 0028-0836 Impact factor: 49.962