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Horm Behav. 2019 May;111:60-69. doi: 10.1016/j.yhbeh.2018.10.011. Epub 2018 Nov 8.

Oxytocin receptor knockout prairie voles generated by CRISPR/Cas9 editing show reduced preference for social novelty and exaggerated repetitive behaviors.

Author information

1
Laboratory of Molecular Biology, Department of Molecular and Cell Biology, Graduate School of Agricultural Science, Tohoku University, 468-1, Aramaki Aza-Aoba, Aoba-ku, Sendai 980-0845, Miyagi, Japan.
2
Silvio O. Conte Center for Oxytocin and Social Cognition, Center for Translational Social Neuroscience, Yerkes National Primate Research Center, Emory University, Atlanta, USA.
3
Department of Obstetrics and Gynecology, Juntendo University, 2-1-1, Hongo, Bunkyo-ku, Tokyo 113-8421, Japan.
4
Silvio O. Conte Center for Oxytocin and Social Cognition, Center for Translational Social Neuroscience, Yerkes National Primate Research Center, Emory University, Atlanta, USA; Center for Social Neural Networks, University of Tsukuba, Tsukuba, Japan; Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, USA. Electronic address: lyoun03@emory.edu.
5
Laboratory of Molecular Biology, Department of Molecular and Cell Biology, Graduate School of Agricultural Science, Tohoku University, 468-1, Aramaki Aza-Aoba, Aoba-ku, Sendai 980-0845, Miyagi, Japan. Electronic address: knishimori@m.tohoku.ac.jp.

Abstract

Behavioral neuroendocrinology has benefited tremendously from the use of a wide range of model organisms that are ideally suited for particular questions. However, in recent years the ability to manipulate the genomes of laboratory strains of mice has led to rapid advances in our understanding of the role of specific genes, circuits and neural populations in regulating behavior. While genome manipulation in mice has been a boon for behavioral neuroscience, the intensive focus on the mouse restricts the diversity in behavioral questions that can be investigated using state-of-the-art techniques. The CRISPR/Cas9 system has great potential for efficiently generating mutants in non-traditional animal models and consequently to reinvigorate comparative behavioral neuroendocrinology. Here we describe the efficient generation of oxytocin receptor (Oxtr) mutant prairie voles (Microtus ochrogaster) using the CRISPR/Cas9 system, and describe initial behavioral phenotyping focusing on behaviors relevant to autism. Oxtr mutant male voles show no disruption in pup ultrasonic vocalization, anxiety as measured by the open field test, alloparental behavior, or sociability in the three chamber test. Mutants did however show a modest elevation in repetitive behavior in the marble burying test, and an impairment in preference for social novelty. The ability to efficiently generate targeted mutations in the prairie vole genome will greatly expand the utility of this model organism for discovering the genetic and circuit mechanisms underlying complex social behaviors, and serves as a proof of principle for expanding this approach to other non-traditional model organisms.

KEYWORDS:

Autism spectrum disorder; CRISPR/Cas9; Genome editing; Non-traditional models; Oxytocin receptor; Prairie voles; Social behavior; Social novelty preference

PMID:
30713102
PMCID:
PMC6506400
[Available on 2020-05-01]
DOI:
10.1016/j.yhbeh.2018.10.011

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