OECD 488: Transgenic rodent somatic and germ cell gene mutation assays (Muta™Mouse)
The Transgenic Rodent (TGR) Mutation Assays can detect chemicals that induce point mutations and small deletions (as opposed to gross chromosomal damage/loss) in somatic and germ cells in vivo. TGR mutation models contain transgenic reporter genes that are carried on vectors designed to be easily recovered from any tissue in the body. Mutations arising in a rodent are measured by recovering and analyzing the phenotype of the reporter gene in a bacterial host deficient for the reporter gene.
Muta™Mouse is a transgenic mouse model that contains multiple copies of the lacZ reporter gene in a single locus on chromosome 3. DNA is isolated from tissues of interest, then the reporter gene is excised and inserted into phage particles. These are incubated with E. coli bacteria that lack both a functional lacZ gene and a functional galE gene (galE−, lacZ−). The bacteria are grown on selective medium that is toxic to galE−, lacZ− bacteria. Only bacteria with a back-mutated, functional lacZ+ gene can survive. The mutation frequency can be estimated by the ratio of the number of bacterial colonies growing on the selective medium to those on non-selective medium.