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

Hui Z. Mao, Evanthia T. Roussos, Miklós Péterfy

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)440-446
Number of pages7
JournalBiochimica et Biophysica Acta - Molecular Basis of Disease
Volume1762
Issue number4
DOIs
StatePublished - Apr 1 2006

Keywords

  • Animal model
  • C57BLKS mouse strain
  • Leptin receptor mutation
  • Microsatellite marker
  • Type 2 diabetes mellitus

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology

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