Chow fed UC Davis strain female Lepr fatty Zucker rats exhibit mild glucose intolerance, hypertriglyceridemia, and increased urine volume, all reduced by a Brown Norway strain chromosome 1 congenic donor region.
Chow fed UC Davis strain female Lepr fatty Zucker rats exhibit mild glucose intolerance, hypertriglyceridemia, and increased urine volume, all reduced by a Brown Norway strain chromosome 1 congenic donor region.
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DOI：
10.1371/journal.pone.0188175
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Stern JS
中科院分区：
文献类型：
--
作者：
Warden CH;Bettaieb A;Min E;Fisler JS;Haj FG;Stern JS
我们的目标是确定影响肥胖动物2型糖尿病（T2D）或肾脏疾病任何表型发展的基因。我们使用生殖分离的UC Davis脂肪Zucker菌株大鼠模型，其中4号染色体瘦素受体（LeprfaSte/faSte）缺陷导致脂肪性肥胖。我们之前在Zucker （ZUC）背景下从Brown Norway菌株（BN）中获得了1号染色体远端一半的同源菌株（BN. zuck - d1rat183 - d1rat90）。先前在男性中发表的研究表明，BN基因供体区域保护某些表型的肾功能障碍和T2D。我们现在将研究范围扩大到女性，并将表型分析扩展到基因表达。我们进行了糖尿病和肾脏疾病的表型研究的雌性BN。以zucc - d1rat183 - d1rat90基因菌株确定UC Davis模型的具体特征。基因供体区BN和ZUC基因型的肥胖LeprfaSte/faSte动物在葡萄糖耐量试验后2小时的空腹血糖和血糖水平均为糖尿病前期水平。我们在肥胖女性中观察到明显的同源菌株1号染色体基因型效应，导致食物摄入量、尿量、葡萄糖耐量试验曲线下葡萄糖面积、血浆甘油三酯水平和每天尿糖排泄量减少。在肥胖雌性中，同源菌株BN基因型对非空腹血浆尿素氮、甘油三酯和肌酐有显著影响。6个基因均位于1号染色体BN供体区，对T2D或肾功能有潜在影响。结果与BN基因型1号染色体基因区影响肥胖UC Davis ZUC女性2型糖尿病和肾功能性状的假设一致，并且存在许多位置候选基因。
Our objective is to identify genes that influence the development of any phenotypes of type 2 diabetes (T2D) or kidney disease in obese animals. We use the reproductively isolated UC Davis fatty Zucker strain rat model in which the defective chromosome 4 leptin receptor (LeprfaSte/faSte) results in fatty obesity. We previously produced a congenic strain with the distal half of chromosome 1 from the Brown Norway strain (BN) on a Zucker (ZUC) background (BN.ZUC-D1Rat183–D1Rat90). Previously published studies in males showed that the BN congenic donor region protects from some phenotypes of renal dysfunction and T2D. We now expand our studies to include females and expand phenotyping to gene expression. We performed diabetes and kidney disease phenotyping in chow-fed females of the BN.ZUC-D1Rat183-D1Rat90 congenic strain to determine the specific characteristics of the UC Davis model. Fatty LeprfaSte/faSte animals of both BN and ZUC genotype in the congenic donor region had prediabetic levels of fasting blood glucose and blood glucose 2 hours after a glucose tolerance test. We observed significant congenic strain chromosome 1 genotype effects of the BN donor region in fatty females that resulted in decreased food intake, urine volume, glucose area under the curve during glucose tolerance test, plasma triglyceride levels, and urine glucose excretion per day. In fatty females, there were significant congenic strain BN genotype effects on non-fasted plasma urea nitrogen, triglyceride, and creatinine. Congenic region genotype effects were observed by quantitative PCR of mRNA from the kidney for six genes, all located in the chromosome 1 BN donor region, with potential effects on T2D or kidney function. The results are consistent with the hypothesis that the BN genotype chromosome 1 congenic region influences traits of both type 2 diabetes and kidney function in fatty UC Davis ZUC females and that there are many positional candidate genes.
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影响因子：
4.6
作者：
Hsu MF;Bettaieb A;Ito Y;Graham J;Havel PJ;Haj FG
通讯作者：
Haj FG
影响因子：
2.9
作者：
Kessler, MA;Meinitzer, A;Wolfbeis, OS
通讯作者：
Wolfbeis, OS
影响因子：
4
作者：
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影响因子：
19.6
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Peterson, R.
影响因子：
2.1
作者：
Fram, Ethan B.;Moazami, Saman;Stern, Joshua M.
通讯作者：
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