The effects of methyl-donor deficiency on mutation induction and transgenerational instability in mice

Mutation Research
Mariel VoutounouYuri E Dubrova

Abstract

The results of recent human and animal studies have provided strong evidence for the epigenetic effects of a dietary deficiency of methyl donors such as folate, choline and methionine on cancer risk and some other common diseases. However, the mechanisms underlying the links between epigenetic alterations and disease remain elusive. To establish whether a methyl-donor deficient diet can result in long-term changes in mutation rate in treated animals and their offspring, BALB/c male mice were maintained for 8 weeks, from 4 weeks of age, on a synthetic diet lacking in choline and folic acid. Using single-molecule PCR, the frequency of mutation at the mouse expanded simple tandem repeat (ESTR) locus Ms6-hm was established in sperm samples of treated males, as well as in sperm and brain of their first-generation offspring. ESTR mutation frequency in the germline of males sacrificed immediately after treatment or sampled 6 and 10 weeks after the end of dietary restriction did not significantly differ from that in age-matched control groups. The frequency of ESTR mutation in DNA samples extracted from sperm and brain of the first-generation offspring of treated mice was also similar to that in controls. The results of our study sugge...Continue Reading

References

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Feb 7, 2012·Proceedings of the National Academy of Sciences of the United States of America·Colin D Glen, Yuri E Dubrova

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Citations

Dec 10, 2014·Molecular Nutrition & Food Research·Colin D GlenYuri E Dubrova
Jul 16, 2015·Mutation Research·Amanda J MacFarlaneCarole L Yauk
Apr 10, 2015·Genetics·Carrie Deans, Keith A Maggert

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