Development and analysis of model rats for diseases of endocrinology and metabolism

采用ENU （n -乙基-n -亚硝基脲）诱变方法，培养了瘦素基因Q92X无义突变的瘦素缺陷大鼠Lep^(mkyo)/Lep^（mkyo）。Lep^(mkyo)/Lep^（mkyo）大鼠显示肥胖表型，包括脂肪肝，与Lepob/Lepobmice相当。Lep^(mkyo)/Lep^（mkyo）大鼠是可治疗的缺乏瘦素信号的大鼠模型，将进一步了解肥胖及其并发症。Berardinelli-Seip先天性脂肪营养不良2基因（BSCL2）突变是先天性广泛性脂肪营养不良2型患者的潜在缺陷。采用ENU （n -乙基-n -亚硝基脲）诱变的方法，我们在BSCL2中产生了一个过早停止密码子（L20X）的seipin缺陷（seipin KO）大鼠。本研究清楚地揭示了seipin不仅在脂肪组织中，而且在脑和睾丸中的生理作用。

Using the method with ENU (N-ethyl-N-nitrosourea) mutagenesis, we generated a leptin deficient Lep^(mkyo)/Lep^(mkyo)rat that had a nonsense mutation (Q92X) in leptin gene. Lep^(mkyo)/Lep^(mkyo)rats showed obese phenotypes including fatty liver, which werecomparable to Lepob/Lepobmice. Lep^(mkyo)/Lep^(mkyo) rat is the treatable rat model lacking leptin signal and will bring further understanding of obesity and its complications.Mutations in the Berardinelli-Seip congenital lipodystrophy 2 gene (BSCL2) are the underlying defect in patients with congenital generalized lipodystrophy type 2. Using the method with ENU (N-ethyl-N-nitrosourea) mutagenesis, we generated a seipin deficient (seipin KO) rat that had a premature stop codon (L20X) in BSCL2. The present study clearly revealed the physiological roles of seipin not only in adipose tissue but also brain and testis.