CRISPR-Cas9 editing of the arginine–vasopressin V1a receptor produces paradoxical changes in social behavior in Syrian hamsters

Taylor J.H.; Walton J.C.; McCann K.E.Norvelle A.LiuQ.Ver Velden J.W.Borl J.M.

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CRISPR-Cas9 editing of the arginine–vasopressin V1a receptor produces paradoxical changes in social behavior in Syrian hamsters

机译：CRISPR-Cas9 editing of the arginine–vasopressin V1a receptor produces paradoxical changes in social behavior in Syrian hamsters

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Studies from a variety of species indicate that arginine–vasopressin (AVP) and its V1a receptor (Avpr1a) play a critical role in the regulation of a range of social behaviors by their actions in the social behavior neural network. To further investigate the role of AVPRs in social behavior, we performed CRISPR-Cas9–mediated editing at the Avpr1a gene via pronuclear microinjections in Syrian hamsters (Mesocricetus auratus), a species used extensively in behavioral neuroendocrinology because they produce a rich suite of social behaviors. Using this germ-line gene-editing approach, we generated a stable line of hamsters with a frame-shift mutation in the Avpr1a gene resulting in the null expression of functional Avpr1as. Avpr1a knockout (KO) hamsters exhibited a complete lack of Avpr1a-specific autoradiographic binding throughout the brain, behavioral insensitivity to centrally administered AVP, and no pressor response to a peripherally injected Avpr1a-specific agonist, thus confirming the absence of functional Avpr1as in the brain and periphery. Contradictory to expectations, Avpr1a KO hamsters exhibited substantially higher levels of conspecific social communication (i.e., odor-stimulated flank marking) than their wild-type (WT) littermates. Furthermore, sex differences in aggression were absent, as both male and female KOs exhibited more aggression toward same-sex conspecifics than did their WT littermates. Taken together, these data emphasize the importance of comparative studies employing gene-editing approaches and suggest the startling possibility that Avpr1a-specific modulation of the social behavior neural network may be more inhibitory than permissive.

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《Proceedings of the National Academy of Sciences of the United States of America.》 |2022年第19期|e2121037119-e2121037119|共1页
作者
Taylor J.H.; Walton J.C.; McCann K.E.Norvelle A.LiuQ.Ver Velden J.W.Borl J.M.;
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作者单位

Neuroscience Institute, Georgia State University, Atlanta, GA 30303, United States;

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收录信息美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
原文格式 PDF
正文语种英语
中图分类自然科学总论;
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aggression; flank marking; oxytocin; social behavior neural network; social communication;

CRISPR-Cas9 editing of the arginine–vasopressin V1a receptor produces paradoxical changes in social behavior in Syrian hamsters

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