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. ? ?
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