Effect of SCID mutation on the occurrence of mouse Pc-1 (Ms6-hm) germline mutations.

Mouse Pc-1 (Ms6-hm) is a hypervariable minisatellite locus that is unstableduring intergenerational transmission. This hyper-instability of Pc-1 isuseful for detecting germline mutation using a small number of experimentalanimals, although its molecular mechanism has not yet been elucidated. Weexamined the effect of severe combined immune deficiency (SCID) mutation onthe spontaneous germline mutation at the Pc-1 locus using the CB17 mousestrain. Our results showed that the frequency of spontaneous germlinemutation at Pc-1 in the offspring of wild-type parents was 9.7%.In F1between SCID male and wild-type female, however, the frequency of germlinemutation was drastically increased to 42.3%. When SCID female mice were mated with wild-type male, the frequency of germline mutation in F1 was slightly increased to 13.6%. These results suggest that DNA protein kinase catalytic subunit (DNA-PKcs), deficiency of which causes SCID mutation, plays an important role in the stable transmission of a genome containing hypervariable tandem repeats to progeny in male germ cells