Mus musculus : Genetic Portrait of the House Mouse Reference

role in the study of genetics ever since Carl Correns, Hugo De Vries, and Erich Von Tschermak independently rediscovered Mendel’s laws at the beginning of the twentieth century. Because these three scientists, as well as Mendel himself, performed their research entirely on plants, many in the scientific community questioned whether Mendel’s laws could explain the basis for inheritance in animals, especially humans. The reason for this skepticism is easy to see. People, for example, differ in the expression of many commonly inherited traits— such as skin color, eye color, curliness of hair, and height—that show no evidence of transmission according to Mendel’s laws. We now know that these traits result from the interaction of many genes with multiple alleles that each segregate according to Mendel’s first law even though the traits themselves do not. At the beginning of the twentieth century, however, a demonstration of the applicability of Mendel’s laws to animal inheritance required the analysis of simple traits controlled by single genes. M. musculus has many features that enhance its value as a model organism for genetic analysis, and foremost among these is the availability of hundreds of singlegene mutations. These mutations arose during the mouse’s long history of domestication as a pet. Over the centuries, dealers in what became known as the “fancy mouse” trade selected and bred mice with numerous coat colors and other visible mutations, first in China and Japan, later in Europe (Fig. E.1a). In contrast to the variation that occurs naturally in wild populations, new traits that appear suddenly in captive-bred mice are almost always the result of single-gene mutations. Early animal geneticists made note of this fact and used fancy mice to demonstrate that Mendel’s laws apply to mammals and, by extrapolation, to humans. In addition to providing a ready source of single-gene mutations, the house mouse has several other features that make it the mammal of choice for genetic analysis. Mice have a very short generation time of just eight to nine weeks. They are small enough so that thousands can live in relatively small rooms. They have large litters of eight or more pups. They breed readily in captivity. Fathers do not harm their young. And after centuries of artificial selection, domesticated mice are docile and easy to handle (Fig. E.1b). But why study a mammal at all when animals like fruit flies and nematodes are even smaller and more amenable to genetic analysis? The answer is that a major goal of current biological research is the understanding of human beings. And although many features of human biology, especially at the cellular and molecular levels, are common to a broad spectrum of life-forms, the most advanced organismlevel human characteristics appear in a limited subset of animals. In fact, many aspects of human development and disease are common only to placenta-bearing mammals such as the mouse. Thus, the mouse provides a powerful model system for investigating the genetic basis of simple and complex human traits, especially those related to development and disease (Fig. E.2). Two general themes emerge from our presentation of M. musculus. First, because of the many similarities between mouse and human genomes, researchers can use Mus musculus: Genetic Portrait of the House Mouse ReferenceE