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对43个近交系小鼠品系进行的多种性状测量捕捉到了人类群体特有的表型多样性。

Multiple trait measurements in 43 inbred mouse strains capture the phenotypic diversity characteristic of human populations.

作者信息

Svenson Karen L, Von Smith Randy, Magnani Phyllis A, Suetin Heather R, Paigen Beverly, Naggert Jürgen K, Li Renhua, Churchill Gary A, Peters Luanne L

机构信息

The Jackson Laboratory, 600 Main St., Bar Harbor, ME 04609, USA.

出版信息

J Appl Physiol (1985). 2007 Jun;102(6):2369-78. doi: 10.1152/japplphysiol.01077.2006. Epub 2007 Feb 22.

Abstract

The breadth of genetic and phenotypic variation among inbred strains is often underappreciated because assessments include only a limited number of strains. Evaluation of a larger collection of inbred strains provides not only a greater understanding of this variation but collectively mimics much of the variation observed in human populations. We used a high-throughput phenotyping protocol to measure females and males of 43 inbred strains for body composition (weight, fat, lean tissue mass, and bone mineral density), plasma triglycerides, high-density lipoprotein and total cholesterol, glucose, insulin, and leptin levels while mice consumed a high-fat, high-cholesterol diet. Mice were fed a chow diet until they were 6-8 wk old and then fed the high-fat diet for an additional 18 wk. As expected, broad phenotypic diversity was observed among these strains. Significant variation between the sexes was also observed for most traits measured. Additionally, the response to the high-fat diet differed considerably among many strains. By the testing of such a large set of inbred strains for many traits, multiple phenotypes can be considered simultaneously and thereby aid in the selection of certain inbred strains as models for complex human diseases. These data are publicly available in the web-accessible Mouse Phenome Database (http://www.jax.org/phenome), an effort established to promote systematic characterization of biochemical and behavioral phenotypes of commonly used and genetically diverse inbred mouse strains. Data generated by this effort builds on the value of inbred mouse strains as a powerful tool for biomedical research.

摘要

近交系之间遗传和表型变异的广度常常未得到充分认识,因为评估仅涵盖有限数量的品系。对更多近交系进行评估不仅能让我们更好地理解这种变异,而且总体上能模拟人类群体中观察到的许多变异。我们采用高通量表型分析方案,在小鼠食用高脂、高胆固醇饮食时,测量了43个近交系雌雄小鼠的身体组成(体重、脂肪、瘦组织质量和骨矿物质密度)、血浆甘油三酯、高密度脂蛋白和总胆固醇、葡萄糖、胰岛素及瘦素水平。小鼠在6 - 8周龄前喂食普通饲料,之后再喂食高脂饲料18周。正如预期的那样,在这些品系中观察到了广泛的表型多样性。对于所测量的大多数性状,两性之间也存在显著差异。此外,许多品系对高脂饮食的反应差异很大。通过对如此大量近交系的多种性状进行测试,可以同时考虑多种表型,从而有助于选择某些近交系作为复杂人类疾病的模型。这些数据可在可通过网络访问的小鼠表型数据库(http://www.jax.org/phenome)中公开获取,该数据库旨在促进对常用且基因多样的近交小鼠品系的生化和行为表型进行系统表征。这项工作所产生的数据建立在近交小鼠品系作为生物医学研究强大工具的价值之上。

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