O. Niwa et R. Kominami, Untargeted mutation of the maternally derived mouse hypervariable minisatellite allele in F-1 mice born to irradiated spermatozoa, P NAS US, 98(4), 2001, pp. 1705-1710
Citations number
40
Categorie Soggetti
Multidisciplinary
Journal title
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Length change mutation at the Ms6hm hypervariable mouse minisatellite locus
was analyzed in C57BL/6N x C3H/HeN F-1 mice and the F-1 of the reciprocal
cross born to irradiated male parents. Spontaneous mutant frequencies were
8.4% and 9.8% for the paternally derived and maternally derived C3H/HeN all
eles, respectively. The mutant frequencies for the paternally derived allel
e increased to 22% and 19% when the male parents were irradiated with 6 Gy
at the postmeiotic spermatozoa stage and the spermatogonia stage, respectiv
ely. These increases in the mutant frequency were at least 10 to 100 times
higher than those expected from the frequency of hits to the 3- to 4-kb all
ele, suggesting that the length change mutation at this minisatellite locus
was not a targeted event due directly to DNA damage in the region. Further
analysis demonstrated that the mutant frequency increased also at the mate
rnally derived C3H/HeN allele to 20% when the male parents were irradiated
at the spermatozoa stage. This increase in the maternal allele mutation was
not observed in F-1 born to irradiated spermatogonia, The present study su
ggests that introduction of DNA damage by irradiated sperm triggers genomic
instability in zygotes and in embryos of subsequent developmental stages,
and this genomic instability induces untargeted mutation in cis at the pate
rnally derived minisatellite allele and in trans at the maternally derived
unirradiated allele. Untargeted mutation revealed in the present study defi
nes a previously unnoticed genetic hazard to the maternally derived genome
by the paternally introduced DNA damage.