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Affected individuals almost completely lack adipose tissue and suffer from severe diabetes and metabolic complications. Likewise, mice lacking <jats:italic>Bscl2<\/jats:italic> in all tissues have dramatically reduced adipose mass, glucose intolerance and hyperinsulinaemia. However, male adipose tissue-specific <jats:italic>Bscl2<\/jats:italic> knockout mice fail to develop the metabolic dysfunction observed in <jats:italic>Bscl2<\/jats:italic> null mice and <jats:italic>BSCL2<\/jats:italic> deficient patients, despite a similar generalised lack of adipose tissues. Clinical reports indicate gender differences frequently exist in cases of lipodystrophy, with female patients more adversely affected than male patients. We therefore generated and characterised female mice lacking <jats:italic>Bscl2<\/jats:italic> specifically in adipose tissue (Ad-B2<jats:sup>(\u2212\/\u2212)<\/jats:sup>). We show that female Ad-B2<jats:sup>(\u2212\/\u2212)<\/jats:sup> mice also develop early-onset lipodystrophy when fed a chow diet and are maintained under standard housing conditions (21\u2009\u00b0C) or thermoneutrality (30\u2009\u00b0C). Despite this, female Ad-B2<jats:sup>(\u2212\/\u2212)<\/jats:sup> mice fail to develop severe metabolic dysfunction. Only when female Ad-B2<jats:sup>(\u2212\/\u2212)<\/jats:sup> mice are maintained at thermoneutrality and fed a high-fat diet do subtle alterations to metabolic homeostasis manifest. This is despite a striking inability to expand adipose mass. Our findings provide further evidence that loss of <jats:italic>Bscl2<\/jats:italic> in non-adipose tissues may contribute to the severity of metabolic dysfunction in this condition.<\/jats:p>","DOI":"10.1038\/s41598-018-36078-9","type":"journal-article","created":{"date-parts":[[2018,12,10]],"date-time":"2018-12-10T14:23:26Z","timestamp":1544451806000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Female adipose tissue-specific Bscl2 knockout mice develop only moderate metabolic dysfunction when housed at thermoneutrality and fed a high-fat diet"],"prefix":"10.1038","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4230-4355","authenticated-orcid":false,"given":"George D.","family":"Mcilroy","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sharon E.","family":"Mitchell","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Weiping","family":"Han","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mirela","family":"Delibegovi\u0107","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5020-4939","authenticated-orcid":false,"given":"Justin J.","family":"Rochford","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2018,12,14]]},"reference":[{"key":"36078_CR1","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1677\/JOE-10-0272","volume":"207","author":"I Huang-Doran","year":"2010","unstructured":"Huang-Doran, I., Sleigh, A., Rochford, J. 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