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This copy number variation includes a 3.0\u2009Mb deletion and a nested proximal 1.5\u2009Mb hemizygous deletion in the same region. Evidence indicates that the distal 22q11.2 region outside the nested 1.5\u2009Mb deletion also might be contributory in humans. However, the precise genetic architecture within the distal region responsible for psychiatric disorders remains unclear, and this issue cannot be experimentally evaluated beyond the correlation in humans. As <jats:italic>CRKL<\/jats:italic> (CRK\u2010like Proto\u2010Oncogene, Adaptor Protein<jats:italic>)<\/jats:italic> is one of the genes encoded in the distal 22q11.2 segment and its homozygous deletion causes physical phenotypes of 22q11.2 hemizygous deletion, we tested the hypothesis that its murine homolog <jats:italic>Crkl<\/jats:italic> contributes to behavioral phenotypes relevant to psychiatric disorders in mice. Congenic <jats:italic>Crkl<\/jats:italic> heterozygosity reduced thigmotaxis, an anxiety\u2010related behavior, in an inescapable open field, but had no apparent effect on social interaction, spontaneous alternation in a T\u2010maze, anxiety\u2010like behavior in an elevated plus maze, or motor activity in an open field. Our data indicate that the heterozygosity of murine <jats:italic>Crkl<\/jats:italic> does not recapitulate social deficits, working memory deficits, repetitive behavior traits or hyperactivity of human 22q11.2 hemizygous deletion. Moreover, while 22q11.2 hemizygous deletion is associated with high levels of phobia and anxiety in humans, our data suggest that <jats:italic>Crkl<\/jats:italic> heterozygosity rather acts as a protective factor for phobia\u2010like behavior in an open field.<\/jats:p>","DOI":"10.1111\/gbb.12719","type":"journal-article","created":{"date-parts":[[2020,12,3]],"date-time":"2020-12-03T04:59:36Z","timestamp":1606971576000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Heterozygosity of murine <i>Crkl<\/i> does not recapitulate behavioral dimensions of human 22q11.2 hemizygosity"],"prefix":"10.1111","volume":"20","author":[{"given":"Takahira","family":"Yamauchi","sequence":"first","affiliation":[{"name":"Department of Pharmacology University of Texas Health Science Center at San Antonio  San Antonio Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gina","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of Pharmacology University of Texas Health Science Center at San Antonio  San Antonio Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6846-5969","authenticated-orcid":false,"given":"Noboru","family":"Hiroi","sequence":"additional","affiliation":[{"name":"Department of Pharmacology University of Texas Health Science Center at San Antonio  San Antonio Texas"},{"name":"Department of Cellular and Integrative Physiology University of Texas Health Science Center at San Antonio  San Antonio Texas"},{"name":"Department of Cell Systems and Anatomy University of Texas Health Science Center at San Antonio  San Antonio 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