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Inactivation of mutant <jats:italic>HTT<\/jats:italic> selectively in the hypothalamus prevents the development of metabolic dysfunction and depressive-like behavior in the BACHD mouse model. The hypothalamic paraventricular nucleus (PVN) is implicated in metabolic and emotional control, therefore we here tested whether inactivation of mutant <jats:italic>HTT<\/jats:italic> in the PVN affects metabolic and psychiatric manifestations of HD in BACHD mice. BACHD mice were crossed with mice expressing Cre-recombinase under the Sim1 promoter (Sim1-Cre) to inactivate mutant <jats:italic>HTT<\/jats:italic> in Sim1 expressing cells, i.e. the PVN of the hypothalamus. We found that inactivation of mutant <jats:italic>HTT<\/jats:italic> in Sim1 cells had a sex-specific effect on both the metabolic and the psychiatric phenotype, as these phenotypes were no longer different in male BACHD\/Sim1-Cre mice compared to wild-type littermates. We also found a reduced number of GnRH neurons specifically in the anterior hypothalamus and an increased testes weight in male BACHD mice compared to wild-type littermates. Taken together, expression of mutant HTT in Sim1 cells may play a role for the development of metabolic dysfunction and depressive-like behavior in male BACHD mice.<\/jats:p>","DOI":"10.1038\/srep28322","type":"journal-article","created":{"date-parts":[[2016,6,23]],"date-time":"2016-06-23T09:19:34Z","timestamp":1466673574000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Metabolic and behavioral effects of mutant huntingtin deletion in Sim1 neurons in the BACHD mouse model of Huntington\u2019s disease"],"prefix":"10.1038","volume":"6","author":[{"given":"Rana","family":"Soylu-Kucharz","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Baldo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00c5sa","family":"Peters\u00e9n","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2016,6,23]]},"reference":[{"issue":"6","key":"BFsrep28322_CR1","doi-asserted-by":"publisher","first-page":"971","DOI":"10.1016\/0092-8674(93)90585-E","volume":"72","author":"M MACDONALD","year":"1993","unstructured":"HDCRG. 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