Genetic and Cellular Effects In Mice Selected For Age-Specific Growth

Abstract

The purpose of this research is to better characterize the origin and evolution of mammalian development. This topic is addressed by examining maternal effects, temporal genetic effects, and hepatocyte endopolyploidy and their impact on mouse growth. This dissertation starts with a discussion of several well-characterized maternal effects and each effect's influence on offspring's growth, gene expression, reproduction, behavior, and disease incidence, among other traits. The role of maternal effects in the evolution of quantitative traits is discussed, as well as the interaction between maternal effects and genomic imprinting in mammals.

Growth during ontogeny is characterized by different cellular mechanisms and may be influenced by different sets of genes acting at different ages. To further investigate the differential genetic control of growth during ontogeny, quantitative trait loci (QTL) analysis was performed to search for chromosomal regions influencing growth in two F2 populations produced from four mouse strains. These four strains are derived from an age-specific restricted index selection project, which has lead to differences in rate of development in body weight, as well as differences in cell number and cell size. Chromosomal regions influencing growth during ontogeny do not overlap between the two populations, suggesting age-specific growth is influenced by different sets of loci, as hypothesized. Epistatic interactions partially overlap between populations, suggesting growth throughout ontogeny shares some aspect of genetic architecture.

In some species, evolution in quantitative traits is associated with variation in endopolyploidy, or the generation of polyploid cells by DNA replication without subsequent cell division. Given that variation in endopolyploidy affects phenotypic variation, genetic selection for a quantitative trait could alter onset and extent of mammalian endopolyploidy. Flow cytometry is used to characterize hepatic cellular changes as a correlated response to selection for age-specific growth, using the same four mouse strains described above. Polyploid cell frequency within each line increased as ontogeny progressed, as expected from previous research. Selection for divergence in early growth only temporarily changes liver endopolyploidy. However, selection for hypertrophic growth has lead to significant changes in polyploidy frequency, starting at weaning and continuing into adulthood.