EARLY HUSBANDRY INFLUENCES ON ADULT PHENOTYPE

描述（由申请人提供）：人类健康的重大进展将来自对基因组功能的理解。不幸的是，许多表型对于遗传分析来说变化太大了。表型是遗传因素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。该项目专注于两种表型，即使在近亲繁殖的小鼠中也是高度可变的；口味偏好和饮食引起的肥胖。目的是评估一些早期生活实验室变量对这些成年表型的贡献。早期操纵的变量将是(1)凋落物大小和组成。这一目标背后的假设是，一个或多个与小鼠与其窝友（包括子宫内和子宫外）相互作用有关的因素对其表型产生终身影响。该方法将涉及比较来自不同大小和性别比例的幼鼠的成年表型。(2)新生儿和断奶期饮食。这一目的背后的假设是，小鼠在断奶前和断奶期间摄入的不受控制的饮食方面影响成年表型变异性。该方法将比较幼年时饲喂不同饮食的成年小鼠的表型。(3)从育种单位到试验机构运输过程中起作用的因素。这一目的背后的假设是，与小鼠从繁殖体到试验点的运输有关的因素是导致成年表型变异的原因。该方法将(a)监测运输过程中的环境参数，(b)系统地评估每个环境参数（例如，食物剥夺，水剥夺，温度，运动）对成虫表型的贡献。提出的研究将描述一些可能对成人表型产生不受控制影响的环境因素。这一结果将有助于在未来的工作中更好地控制环境，并直接导致基因分析更容易、更迅速地取得进展。

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.