TY - JOUR
T1 - Genetic analysis of the diabetes-prone C57BLKS/J mouse strain reveals genetic contribution from multiple strains
AU - Mao, Hui Z.
AU - Roussos, Evanthia T.
AU - Péterfy, Miklós
N1 - Funding Information:
We thank Ed Leiter for providing insights into strain history, Richard C. Davis and Aldons J. Lusis for providing fluorophore-labeled primers, Ping-Zi Wen for assistance with PCRs, and Krisztina Peterfy for artwork in Fig. 1 . This work was supported by NIH grant R01-DK071673.
PY - 2006/4
Y1 - 2006/4
N2 - 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.
AB - 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.
KW - Animal model
KW - C57BLKS mouse strain
KW - Leptin receptor mutation
KW - Microsatellite marker
KW - Type 2 diabetes mellitus
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U2 - 10.1016/j.bbadis.2006.01.002
DO - 10.1016/j.bbadis.2006.01.002
M3 - Article
C2 - 16481151
AN - SCOPUS:33644759358
SN - 0925-4439
VL - 1762
SP - 440
EP - 446
JO - Biochimica et Biophysica Acta - Molecular Basis of Disease
JF - Biochimica et Biophysica Acta - Molecular Basis of Disease
IS - 4
ER -