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Publication : No evidence for cumulative effects in a Dnmt3b hypomorph across multiple generations.

First Author  Youngson NA Year  2013
Journal  Mamm Genome Volume  24
Issue  5-6 Pages  206-17
PubMed ID  23636699 Mgi Jnum  J:198944
Mgi Id  MGI:5499933 Doi  10.1007/s00335-013-9451-5
Citation  Youngson NA, et al. (2013) No evidence for cumulative effects in a Dnmt3b hypomorph across multiple generations. Mamm Genome 24(5-6):206-17
abstractText  Observations of inherited phenotypes that cannot be explained solely through genetic inheritance are increasing. Evidence points to transmission of non-DNA molecules in the gamete as mediators of the phenotypes. However, in most cases it is unclear what the molecules are, with DNA methylation, chromatin proteins, and small RNAs being the most prominent candidates. From a screen to generate novel mouse mutants of genes involved in epigenetic reprogramming, we produced a DNA methyltransferase 3b allele that is missing exon 13. Mice that are homozygous for the mutant allele have smaller stature and reduced viability, with particularly high levels of female post-natal death. Reduced DNA methylation was also detected at telocentric repeats and the X-linked Hprt gene. However, none of the abnormal phenotypes or DNA methylation changes worsened with multiple generations of homozygous mutant inbreeding. This suggests that in our model the abnormalities are reset each generation and the processes of transgenerational epigenetic reprogramming are effective in preventing their inheritance.
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