Msh3 is a limiting factor in the formation of intergenerational CTG expansions in DM1 transgenic mice

Hum Genet. 2006 Jun;119(5):520-6. doi: 10.1007/s00439-006-0164-7. Epub 2006 Mar 22.


The CTG repeat involved in myotonic dystrophy is one of the most unstable trinucleotide repeats. However, the molecular mechanisms underlying this particular form of genetic instability-biased towards expansions-have not yet been completely elucidated. We previously showed, with highly unstable CTG repeat arrays in DM1 transgenic mice, that Msh2 is required for the formation of intergenerational and somatic expansions. To identify the partners of Msh2 in the formation of intergenerational CTG repeat expansions, we investigated the involvement of Msh3 and Msh6, partners of Msh2 in mismatch repair. Transgenic mice with CTG expansions were crossed with Msh3- or Msh6-deficient mice and CTG repeats were analysed after maternal and paternal transmissions. We demonstrated that Msh3 but not Msh6 plays also a key role in the formation of expansions over successive generation. Furthermore, the absence of one Msh3 allele was sufficient to decrease the formation of expansions, indicating that Msh3 is rate-limiting in this process. In the absence of Msh6, the frequency of expansions decreased only in maternal transmissions. However, the significantly lower levels of Msh2 and Msh3 proteins in Msh6 -/- ovaries suggest that the absence of Msh6 may have an indirect effect.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Pair Mismatch / genetics
  • DNA-Binding Proteins / deficiency
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / physiology
  • Female
  • Humans
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • MutS Homolog 3 Protein
  • Myotonic Dystrophy / genetics*
  • Trinucleotide Repeat Expansion / genetics*


  • DNA-Binding Proteins
  • MSH3 protein, human
  • MutS Homolog 3 Protein