Generation of gene targeted rat models with obesity and lipodystrophy for elucidating the mechanism of leptin action

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We generated and characterized a leptin deficient Lep^<mkyo>/Lep^<mkyo> rat that had a nonsense mutation in leptin gene and seipin knockout rat by the method using ENU mutagenesis. TZDs differentially regulated hepatic peroxisome proliferator-activated receptor gamma (PPARg)mRNA expression and body fat distribution between Lep^<ob>/Lep^<ob> mice and Lepmkyo/Lepmkyorats. Weidentified 8 genes those primarily respond to leptin in the liver commonly in rat and mouse. We detected that seipin deficient rat were infertile due to azoospermia and their spatial working memory is impairedalong with brain weight decrease