To study the origin of mutations in the germ cells (egg and sperm) of mice, two kinds of animals have been used by scientists. One is the normal wild-type mouse and the other is a mutant mouse carrying marker genes that are expressed as easily recognizable characteristics, such as a certain hair color or short ears. The mutant mouse is said to be homozygous for the marker gene, ie, it carries a pair of identical marker genes. When the two types of mouse are crossbred, the resulting offspring are heterozygous, ie, they carry one mutant copy of the marker gene and one normal copy of the gene. They appear to be normal due to the recessive nature of the mutant gene. However, when a mutation is induced in a normal gene–perhaps after experimental irradiation, a mutant characteristic appears among a large number of apparently normal siblings because the normal gene is no longer present to produce the normal characteristic.

In any one experiment, 5 to 7 marker genes are used simultaneously as a cost-saving measure. Several millions of mice have been used in the past for this kind of experiment, mainly in the United States and partly in the United Kingdom.

The frequency of radiation-induced mutations in these mouse studies varies among the genes studied. This would not be expected if all of the genes were equally susceptible to radiation effects, but the reason is unkown.