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Hypothalamus-specific Y2-deleted mice showed a significant decrease in body weight and a significant increase in food intake that was associated with increased mRNA levels for the orexigenic NPY and AgRP, as well as the anorexic proopiomelanocortin (POMC) and cocaine- and amphetamine-regulated transcript (CART) in the arcuate nucleus. These hypothalamic changes persisted until at least 34 days after Y2 deletion, yet the effect on body weight and food intake subsided within this time. Plasma concentrations of pancreatic polypeptide and corticosterone were 3- to 5-fold increased in hypothalamus-specific Y2 knockout mice. Germ-line Y2 receptor knockout also produced a significant increase in plasma levels of pancreatic polypeptide. However, these mice differed from conditional knockout mice in that they showed a sustained reduction in body weight and adiposity associated with increased NPY and AgRP but decreased POMC and CART mRNA levels in the arcuate nucleus. The transience of the observed effects on food intake and body weight in the hypothalamus-specific Y2 knockout mice, and the difference of this model from germ-line Y2 knockout mice, underline the importance of conditional models of gene deletion, because developmental, secondary, or extrahypothalamic mechanisms may mask such effects in germ-line knockouts.<\/jats:p>","DOI":"10.1073\/pnas.132043299","type":"journal-article","created":{"date-parts":[[2002,7,28]],"date-time":"2002-07-28T18:26:28Z","timestamp":1027880788000},"page":"8938-8943","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":211,"title":["Important role of hypothalamic Y2 receptors in body weight regulation revealed in conditional knockout mice"],"prefix":"10.1073","volume":"99","author":[{"given":"Amanda","family":"Sainsbury","sequence":"first","affiliation":[{"name":"Neurobiology Program, Garvan Institute of Medical Research, St. Vincent's Hospital, 384 Victoria 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