title: Effect of SCID mutation on the occurrence of mouse Pc-1 (Ms6-hm) germline mutations.
abstract: Mouse Pc-1 (Ms6-hm) is a hypervariable minisatellite locus that is unstable during intergenerational transmission. This hyper-instability of Pc-1 is useful for detecting germline mutation using a small number of experimental animals, although its molecular mechanism has not yet been elucidated. We examined the effect of severe combined immune deficiency (SCID) mutation on the spontaneous germline mutation at the Pc-1 locus using the CB17 mouse strain. Our results showed that the frequency of spontaneous germline mutation at Pc-1 in the offspring of wild-type parents was 9.7%. In F1 between SCID male and wild-type female, however, the frequency of germline mutation 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.
authors.affiliation: Radiation Safety Research Centre, National Institute of Radiological Sciences 4-9-1 Anagawa, Inage, Chiba 263-8555, Japan. m_yam@nirs.go.jp
authors.forename: Masatake
authors.initials: M
authors.lastname: Yamauchi
authors.forename: Mayumi
authors.initials: M
authors.lastname: Nishimura
authors.forename: Satsuki
authors.initials: S
authors.lastname: Tsuji
authors.forename: Minako
authors.initials: M
authors.lastname: Terada
authors.forename: Motoe
authors.initials: M
authors.lastname: Sasanuma
authors.forename: Yoshiya
authors.initials: Y
authors.lastname: Shimada
mesh_terms: D000818:Animals; D020134:Catalytic Domain; D002874:Chromosome Mapping; D004260:DNA Repair; D051747:DNA-Activated Protein Kinase; D004268:DNA-Binding Proteins; D005260:Female; D018095:Germ-Line Mutation; D008297:Male; D051379:Mice; D016513:Mice, SCID / Q000235:genetics*; D018598:Minisatellite Repeats; D017346:Protein Serine-Threonine Kinases / Q000502:physiology
chemical_list: D004268:DNA-Binding Proteins; D051747:DNA-Activated Protein Kinase; D017346:Protein Serine-Threonine Kinases