Genetic stability and germ cell epigenetic instability in the Mtrr mouse model of transgenerational epigenetic inheritance.

Folate metabolism is important for DNA synthesis and repair through its role in the synthesis of the nucleotide thymidine. Mice with a hypomorphic mutation in the gene Mtrr have disrupted folate metabolism and show transgenerational inheritance of developmental abnormalities. We sought to explore if genetic mutations arising in the Mtrr mice may be responsible for the inheritance of these phenotypes. Therefore we sequenced the genomes of six embryos homozygous for the Mtrr mutation at embryonic day (E) 10.5 with developmental abnormalities. These were compared to two control C57Bl/6J embryos at E10.5, which had no developmental phenotypes. C57Bl/6J embryos were used as controls as they have the same genetic background as the mice with Mtrr mutation.