Human minisatellite MS32 (D1S8) displays somatic but not germline instability in transgenic mice.
Human minisatellite MS32 (D1S8) shows instability both in the germline and, at much lower levels, in somatic DNA. To investigate factors that influence somatic and germline mutation, large cosmid-based constructs containing MS32 were introduced into mice, bred to homozygosity and tested for instability in blood and sperm. Analysis of single copy and multicopy transgenic lines revealed somatic mutants occurring at a frequency comparable with that seen in man. As in humans, these mutants arose mainly by simple intra-allelic duplications and deletions. In contrast, analysis of sperm DNA from four different transgenic lines showed no trace of the complex recombination-based germline instability seen in man, even using PCR-based approaches capable of detecting very rare mutants. These data provide further evidence that germline and somatic mutation at human minisatellite MS32 occur via distinct pathways, that a major barrier exists to the transfer of germline instability from humans to mice and that the mouse germline appears to be protected from mitotic instability of the type seen in blood.
Bois
P
P
Department of Genetics, University of Leicester, UK. prsb1@le.ac.uk
Collick
A
A
Brown
J
J
Jeffreys
A J
AJ
D000483:Alleles; D000818:Animals; D015321:Gene Rearrangement; D018095:Germ-Line Mutation; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008822:Mice, Transgenic / Q000235:genetics; D018598:Minisatellite Repeats / Q000235:genetics*; D016133:Polymerase Chain Reaction / Q000379:methods; D019076:Transgenes / Q000235:genetics*