Chapter 96 - Defining the Genetics of Osteoporosis: Using the Mouse to Understand Man

Abstract

This chapter focuses on the normal allelic variation in inbred strains of mice, to understand the BMD trait in humans. In general, mice have become the workhorses of biomedical research because of their ease of breeding and reproductive capacity, their short life span, and the availability of large numbers of genetic markers in the mouse genome. The second feature of inbred strains that makes them powerful genetic and physiologic tools is that an individual inbred strain differs from all other strains. Each strain has its own set of phenotypic characteristics that make it unique and allow innumerable differences in physiologic behavior. One such difference is in the wide variation in BMD among inbred strains. Thus, by choosing two inbred strains that differ in a trait of interest, a cross can be made to enumerate, locate, and define heritability of the genes that contribute to that trait. Mapping “bone density genes” can be extremely productive in F2 mice as there is independent segregation of unlinked genes for this polygenic phenotype. F2 mice provide an invaluable tool for locating and enumerating QTLs, as well as delineating allelic effects. Recombinant inbred (RI) strains are generated by outcrossing two progenitor strains and then intercrossing these F1 hybrids to produce F2 progeny. Congenic strains are generated to test the effect of individual or multiple linked loci from a donor strain placed on the genetic background of a recipient strain. Congenics have recently become extremely valuable tools for bone biologists, not only for studying the quantitative effect of individual QTLs, but also for more complete understanding of the phenotype and its underlying physiology.