The ability to create transgenic, knockout, and knock-in mice has greatly facilitated the study of human genetics, and these techniques illustrate the power of the mouse as a model genetic organism. The common house mouse, Mus musculus, is among the oldest and most valuable subjects for genetic study: it’s small, prolific, and easy to keep, with a short generation time (Figure 14.23).

Foremost among the many advantages that Mus musculus has as a model genetic organism is its close evolutionary relationship to humans. Being a mammal, the mouse is genetically, behaviorally, and physiologically more similar to humans than are other organisms used in genetic studies, making the mouse the model of choice for many studies of human and medical genetics. Other advantages include a short generation time compared with those of most other mammals. Mus musculus is well adapted to life in the laboratory and can be easily raised and bred in cages that require little space; thus, several thousand mice can be raised within the confines of a small laboratory room. Mice have large litters (8–10 pups) and are docile and easy to handle. Finally, a large number of mutations have been isolated and studied in captive-bred mice, providing an important source of variation for genetic analysis.

The production of gametes and reproduction in the mouse are very similar to those processes in humans (see Figure 14.23). Male mice begin producing sperm at puberty and continue sperm production throughout the remainder of their lives. Starting at puberty, female mice go through an estrous cycle about every 4 days. After mating and fertilization, the diploid embryo implants in the uterus. Gestation typically takes about 21 days. Mice reach puberty in about 5 to 6 weeks and will live for about two years. A complete generation can be completed in about 8 weeks.

The mouse genome, which contains about 2.7 billion base pairs of DNA, is similar in size to the human genome. For most human genes, there are homologous genes in the mouse, and the linkage relations of many mouse genes are similar to those in humans. The mouse genome is distributed across 19 pairs of autosomes and one pair of sex chromosomes (see Figure 14.23).

We have already considered three powerful techniques that have been developed for use in the mouse: (1) the creation of transgenic mice by the injection of DNA into a mouse embryo, (2) the ability to disrupt specific genes to create knockout mice, and (3) the ability to insert specific sequences into specific loci. These techniques are made possible by the ability to manipulate the mouse reproductive cycle, including the ability to induce ovulation using hormones, to isolate unfertilized oocytes from the ovary, and to implant fertilized embryos in the uterus of a surrogate mother.

A large number of mouse models of specific human diseases have been created—in some cases, by isolating and inbreeding mice with naturally occurring mutations, and in other cases, by using knockout and knock-in techniques to disable and modify specific genes. Mice tolerate inbreeding well, and inbred strains of mice are easily created by brother–sister mating.