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To evaluate functional equivalency between mouse and human<jats:italic>NR2E1<\/jats:italic>, we generated mice transgenic for a genomic clone spanning the human<jats:italic>NR2E1<\/jats:italic>locus and bred these animals to fierce mice deleted for the corresponding mouse gene. In fierce mutants carrying human<jats:italic>NR2E1<\/jats:italic>, structural brain defects were eliminated and eye abnormalities ameliorated. Excitingly, behavior in these \u201crescue\u201d mice was indistinguishable from controls. Because no artificial promoter was used to drive transgene expression, promoter and regulatory elements within the human<jats:italic>NR2E1<\/jats:italic>clone are functional in mouse. Normal behavior in rescue animals suggests that mechanisms underlying the behavioral abnormalities in fierce mice may also be conserved in humans. Our data support the hypothesis that variation at<jats:italic>NR2E1<\/jats:italic>may contribute to human behavioral disorders. Use of this rescue paradigm with other genes will permit the direct evaluation of human genes hypothesized to play a causal role in psychiatric disease but for which evidence is lacking or equivocal.<\/jats:p>","DOI":"10.1523\/jneurosci.4757-04.2005","type":"journal-article","created":{"date-parts":[[2005,7,6]],"date-time":"2005-07-06T23:53:23Z","timestamp":1120694003000},"page":"6263-6270","source":"Crossref","is-referenced-by-count":47,"title":["Pathological Aggression in \u201cFierce\u201d Mice Corrected by Human Nuclear Receptor 2E1"],"prefix":"10.1523","volume":"25","author":[{"given":"Brett S.","family":"Abrahams","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melvin C. 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