Genetic analysis of the diabetes-prone C57BLKS/J mouse strain reveals genetic contribution from multiple strains

Biochim Biophys Acta. 2006 Apr;1762(4):440-6. doi: 10.1016/j.bbadis.2006.01.002. Epub 2006 Jan 30.

Abstract

The C57BLKS/J (BKS) inbred mouse strain is a widely used animal model of type 2 diabetes. In the presence of the diabetes (db) mutation, obese BKS-db mice develop severe diabetes. Genetic studies of diabetes-susceptibility in this strain are facilitated by the fact that BKS is a genetic composite between the diabetes-resistant C57BL/6J (B6) and susceptible DBA/2J (DBA) strains. On this basis, it has been hypothesized that diabetes-susceptibility in BKS is conferred by DBA-derived alleles. However, recent studies revealed non-B6/non-DBA genetic material in BKS. To identify the origin of this genetic component, we generated a genomic map of BKS using 537 microsatellite markers. Our results demonstrate that, in addition to B6 and DBA, BKS contains alleles from at least three other strains, including 129, C57BL/10 and an unidentified mouse strain. We also analyzed two congenic strains, B6-db and BKS-db, which are widely used for the genetic mapping of diabetes-susceptibility loci. We identified several donor-derived genomic regions introduced during the generation of these congenic strains. In summary, our study reveals novel aspects of the genetic fine-structure of BKS and related strains and facilitates the identification of diabetes-susceptibility loci in this mouse model.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Alleles
  • Animals
  • Crosses, Genetic
  • Diabetes Mellitus, Type 2 / genetics*
  • Disease Models, Animal*
  • Mice
  • Mice, Inbred C57BL / genetics
  • Mice, Inbred DBA / genetics
  • Mice, Inbred Strains / genetics*
  • Mice, Mutant Strains / genetics*
  • Mice, Obese / genetics
  • Microsatellite Repeats
  • Mutation