RT Journal
A1 Uchimura, Arikuni
A1 Higuchi, Mayumi
A1 Minakuchi, Yohei
A1 Ohno, Mizuki
A1 Toyoda, Atsushi
A1 Fujiyama, Asao
A1 Miura, Ikuo
A1 Wakana, Shigeharu
A1 Nishino, Jo
A1 Yagi, Takeshi
T1 Germline mutation rates and the long-term phenotypic effects of mutation accumulation in wild-type laboratory mice and mutator mice
JF Genome Research 
JO Genome Research 
YR 2015 
FD August 01 
VO 25 
IS 8 
SP 1125 
OP 1134 
DO 10.1101/gr.186148.114 
UL http://genome.cshlp.org/content/25/8/1125.abstract 
AB The germline mutation rate is an important parameter that affects the amount of genetic variation and the rate of evolution. However, neither the rate of germline mutations in laboratory mice nor the biological significance of the mutation rate in mammalian populations is clear. Here we studied genome-wide mutation rates and the long-term effects of mutation accumulation on phenotype in more than 20 generations of wild-type C57BL/6 mice and mutator mice, which have high DNA replication error rates. We estimated the base-substitution mutation rate to be 5.4 × 10−9 (95% confidence interval = 4.6 × 10−9–6.5 × 10−9) per nucleotide per generation in C57BL/6 laboratory mice, about half the rate reported in humans. The mutation rate in mutator mice was 17 times that in wild-type mice. Abnormal phenotypes were 4.1-fold more frequent in the mutator lines than in the wild-type lines. After several generations, the mutator mice reproduced at substantially lower rates than the controls, exhibiting low pregnancy rates, lower survival rates, and smaller litter sizes, and many of the breeding lines died out. These results provide fundamental information about mouse genetics and reveal the impact of germline mutation rates on phenotypes in a mammalian population.