A useful variant of the transgenic approach is to produce mice in which a normal gene has been not just mutated, but fully disabled. These animals, called knockout mice, are particularly helpful in determining the function of a gene: the phenotype of the knockout mouse often gives a good indication of the function of the missing gene.

A variant of the knockout procedure is to insert a particular DNA sequence into a known chromosome location. For example, researchers might insert the sequence of a human disease-causing allele into the same locus in mice, creating a precise mouse model of the human disease. Mice that carry inserted sequences at specific locations are called knock-in mice.

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