Genotype x diet interactions in mice predisposed to mammary cancer. I. Body weight and fat
Genotype x diet interactions in mice predisposed to mammary cancer. I. Body weight and fat
复制标题
DOI：
10.1007/s00335-008-9095-z
复制
发表时间：
2008-03-01
期刊：
影响因子：
2.5
通讯作者：
Pomp, Daniel
中科院分区：
文献类型：
--
作者：
Gordon, Ryan R.;Hunter, Kent W.;Pomp, Daniel
高脂肪摄入和肥胖可能会增加对某些癌症的易感性。为了研究膳食脂肪、肥胖和转移性乳腺癌的相互作用，我们建立了一个共分离肥胖QTL和MMTV-PyMT转基因的F-2小鼠群体。我们给F-2小鼠喂食极高脂肪或匹配的对照脂肪饮食，并测量生长、身体组成、乳腺肿瘤发病时的年龄、肿瘤数量和严重程度以及肺转移的形成。基因组中的SNP基因分型促进了QTL和QTL x饮食相互作用效应的分析。在这里，我们描述了由多基因肥胖模型M16 i和FVB/NJ-TgN（MMTV-PyMT）（634 Mul）之间的杂交产生的F-2群体（n = 615）的发展，饮食对生长和身体组成的影响，以及生长和肥胖相关表型的QTL和QTL x饮食和/或性别相互作用效应。我们确定了38个QTL的身体组成性状是显着的，在全基因组0.05水平，可能代表9个不同的位点后，占多效性效应。QTL x饮食和/或性别相互作用存在于这些QTL中的15个，表明这种相互作用在定义复杂性状如体重和肥胖的遗传结构中起着重要作用。
High dietary fat intake and obesity may increase susceptibility to certain forms of cancer. To study the interactions of dietary fat, obesity, and metastatic mammary cancer, we created a population of F-2 mice cosegregating obesity QTL and the MMTV-PyMT transgene. We fed the F-2 mice either a very-high-fat or a matched-control-fat diet and measured growth, body composition, age at mammary tumor onset, tumor number and severity, and formation of pulmonary metastases. SNP genotyping across the genome facilitated analyses of QTL and QTL x diet interaction effects. Here we describe development of the F-2 population (n = 615) which resulted from a cross between the polygenic obesity model M16i and FVB/NJ-TgN (MMTV-PyMT)(634Mul), effects of diet on growth and body composition, and QTL and QTL x diet and/or gender interaction effects for growth and obesity-related phenotypes. We identified 38 QTL for body composition traits that were significant at the genome-wide 0.05 level, likely representing nine distinct loci after accounting for pleiotropic effects. QTL x diet and/or gender interactions were present at 15 of these QTL, indicating that such interactions play a significant role in defining the genetic architecture of complex traits such as body weight and obesity.