Abstract
DNA mismatch repair plays an important role in reducing errors created in DNA replication. Mlh1is one of the genes involved in the mismatch repair. Deficiency of the gene has been shown to result in high frequency of tumor incidence in mice, and also the elevated levels of mutation. Here we wondered when the elevation of mutation appears in the process of mouse development.
The mice used were Mlh1 knockout mice harboring LacZ gene made by crossing with MutaTM mice. The level of mutation frequency at 12 day embryo was higher than those in Mlh1(+/+) or Mlh1(+/-) embryos. The high level was maintained at newborn, adult and middle-aged mice. The molecular characteristics of the mutants in Mlh1 (-/-) showed high frequency of deletion mutation which is unique to mismatch repair deficiency. In an attempt to investigate the consequence of high mutation level in Mlh1(-/-), we examined apoptosis in embryo and newborn mice. Preliminary results showed a low level of apoptosis. These indicate that the deficiency of mismatch repair results in an elevation of mutation at early stage of development and do not affect much in later stages. It is also suggested that the high level of mutation does not interfere with the developmental process in mice.
