Electrophoretic variation in multiple recessive tester, T, stock mice

Area of Science:

• Genetics
• Toxicology
• Mammalian Genetics

Background:

• The mouse specific locus test employs a multiple recessive tester stock, homozygous for seven recessive visible markers, for mutagenicity assessment.
• This stock, developed by W.L. Russell, has a documented history of use since the 1950s across multiple research institutions.
• Stocks are maintained through random mating, with some selected for homozygosity at enzyme and protein markers.

Purpose of the Study:

• To investigate the extent of electrophoretic variation in random-bred and fixed tester stocks.
• To assess genetic variability in mouse stocks used for mutagenicity testing.
• To determine if genetic diversity is maintained over time and across different maintenance centers.

Main Methods:

• Electrophoretic analysis was performed on mouse tester stocks at the MRC Radiobiology Unit (Harwell) and Research Triangle Institute (RTI).
• A total of 44 genetic loci were analyzed for polymorphism.
• Data from 1981 and 1990 were compared to assess changes in genetic variation.

Main Results:

• Eight out of 44 loci (Acy-1, Es-3, Gpi-1, Hba, Hbb, Idh-1, Mod-1, Pgd) exhibited polymorphism at various times.
• Three loci (Es-3, Hbb, Mod-1) showed a decrease in polymorphism, becoming monomorphic by 1990.
• Despite minor losses, the tester stocks retained considerable genetic variability, comparable to wild or other isolated laboratory mouse populations.

Conclusions:

• The mouse tester stocks are considered characteristic of isolated populations, with contamination ruled out.
• The retention of substantial genetic variability is crucial for the effective design of new mutation tests.
• Care must be taken to ensure homozygosity at loci under investigation when utilizing these stocks for mutation testing.