EARLY HUSBANDRY INFLUENCES ON ADULT PHENOTYPE

描述(由申请人提供)：人类健康的重大进步将来自于对基因组功能的了解。不幸的是，对于遗传分析来说，许多表型太过多变。表型是遗传和环境因素共同作用的产物，虽然遗传因素可以非常精确地控制，但环境因素却不能。这是因为影响许多表型的相关环境变量尚未确定。这个项目的重点是两种表型，即使在近亲交配的小鼠中也是高度可变的；口味偏好和饮食诱导的肥胖。我们的目标是评估一些早期生命实验室变量对这些成人表型的贡献。被操纵的早期变量将是(1)产仔数和产仔组成。这一目标背后的假设是，与小鼠与其产仔相互作用(无论是在子宫内还是在子宫外)的一个或多个因素会对其表型产生终身影响。该方法将包括比较来自不同大小和性别比例的小鼠的成体表型。(2)新生儿日粮和断奶日粮。这一目标背后的假设是，小鼠在断奶前和断奶期间摄取的饮食不受控制的方面会影响成年表型的变异性。方法将是比较成年小鼠在幼年时喂食不同食物的表型。(3)从育种者到检测机构的运输过程中的作用因素。这一目标背后的假设是，与小鼠从繁育者到测试地点的运输相关的因素负责诱导成体表型的变异。该方法将是(A)监测运输过程中的环境参数，以及(B)系统地评估每个环境参数(例如，食物缺乏、水缺乏、温度、运动)对成虫表型的贡献。拟议的研究将表征一些环境因素，这些因素可能对成虫表型产生不可控的影响。结果将在未来的工作中带来更好的环境控制，并作为直接结果，在基因分析方面更容易和更快地取得进展。

DESCRIPTION (provided by applicant): Major advances in human health will come from understanding the functions of the genome. Unfortunately, many phenotypes are too variable for genetic analyses. A phenotype is the product of both genetic and environmental factors, and although the genetic ones can be controlled with great precision, the environmental ones cannot. This is because the pertinent environmental variables influencing many phenotypes have not been identified. This project is focused on two phenotypes that are highly variable even in inbred mice; taste preferences and diet-induced obesity. The goal is to assess the contribution of some early life laboratory variables to these adult phenotypes. The early variables manipulated will be (1) litter size and composition. The hypothesis underlying this aim is that one or more factors related to the mouse's interaction with its littermates (both in and ex utero) produces life-long effects on its phenotype. The approach will involve comparing the adult phenotypes of mice originating from litters of different sizes and sex ratios. (2) Neonatal and weaning diet. The hypothesis underlying this aim is that uncontrolled aspects of the diet mice ingest before and during weaning influences adult phenotype variability. The approach will be to compare the phenotypes of adult mice fed various diets when young. (3) Factors acting during shipping from breeder to test institution. The hypothesis underlying this aim is that factors related to the transportation of mice from breeder to test site are responsible for inducing variability in adult phenotype. The approach will be (a) monitor environmental parameters during shipping, and (b) systematically evaluate the contribution of each environmental parameter (e.g., food deprivation, water deprivation, temperature, motion) on adult phenotype. The proposed studies will characterize some environmental factors that may exert uncontrolled effects on adult phenotypes. The results will lead to better environmental controls in future work and, as a direct consequence, easier and more rapid progress with genetic analyses.