Genetic variation among 129 substrains and its importance for targeted mutagenesis in mice

Nat Genet. 1997 May;16(1):19-27. doi: 10.1038/ng0597-19.


Targeted mutagenesis in mice, a powerful tool for the analysis of gene function and human disease, makes extensive use of 129 mouse substrains. Although all are named 129, we document that outcrossing of these substrains, both deliberate and accidental, has lead to extensive genetic variability among substrains and embryonic stem cells derived from them. This clearer understanding of 129 substrain variability allows consideration of its negative impact on targeting technology, including: homologous recombination frequencies, preparation of inbred animals, and availability of appropriate controls. Based on these considerations we suggest a number of recommendations for future experimental design.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Biomarkers
  • Cell Line
  • Crosses, Genetic*
  • Embryo, Mammalian / cytology
  • Female
  • Genetic Variation*
  • Graft Rejection / genetics
  • Male
  • Mice
  • Mice, Inbred C3H
  • Mice, Inbred C57BL
  • Mice, Inbred Strains / genetics*
  • Mice, Mutant Strains
  • Mutagenesis*
  • Polymorphism, Genetic
  • Proteins / genetics
  • Skin Transplantation
  • Stem Cells / cytology


  • Biomarkers
  • Proteins