Genetic analysis of the diabetes-prone C57BLKS/J mouse strain reveals genetic contribution from multiple strains.
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.
Department of Medicine, University of California at Los Angeles, and VA Greater Los Angeles Healthcare System, Los Angeles, CA 90073, USA.
Hui Z
HZ
Mao
Evanthia T
ET
Roussos
Miklós
M
Péterfy
D000483:Alleles; D000818:Animals; D003433:Crosses, Genetic; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D004195:Disease Models, Animal; D051379:Mice; D008810:Mice, Inbred C57BL / Q000235:genetics; D008811:Mice, Inbred DBA / Q000235:genetics; D008815:Mice, Inbred Strains / Q000235:genetics*; D008817:Mice, Mutant Strains / Q000235:genetics*; D008820:Mice, Obese / Q000235:genetics; D018895:Microsatellite Repeats; D009154:Mutation