RRC ID 27732
Author Kose H, Yamada T, Matsumoto K.
Title Single diabetic QTL derived from OLETF rat is a sufficient agent for severe diabetic phenotype in combination with leptin-signaling deficiency.
Journal Exp Diabetes Res
Abstract Obesity has been considered one of the leading causative agents for diseases such as type 2 diabetes, stroke, and heart attack. Due to their complex etiology, establishing a useful animal model is increasingly crucial for better molecular understanding of how obesity influences on disease development. OLETF rat is a spontaneous model of type 2 diabetes. We mapped 14 hyperglycemia QTLs in the genome of the OLETF rat and subsequently generated a panel of congenic strains each possessing OB-R mutation in F344 genetic background. Here we show that one of the loci, Nidd2/of, is highly responsive to obesity. When leptin receptor mutation is introgressed into the Nidd2/of congenic strain, the rat showed hyperglycemia equivalent to that of the parental OLETF rat. This suggests that the Nidd2/of locus has a strong genetic interaction with leptin signaling pathway. Furthermore, when another hyperglycemia QTL Nidd1/of is additionally combined, the strain developed overt diabetes. A single QTL dissected out in spontaneous model normally exerts only mild effect on the quantitative trait, which makes it difficult to clone the gene. Our new model may help not only to identify the causative gene but also to investigate how obesity interacts with a QTL to regulate diabetic traits.
Volume 2012
Pages 858121
Published 2012
DOI 10.1155/2012/858121
PMID 23304119
PMC PMC3529458
MeSH Adiposity / genetics Animals Animals, Congenic Biomarkers / blood Blood Glucose / metabolism Body Weight / genetics Cholesterol / blood Crosses, Genetic Diabetes Mellitus, Type 2 / blood Diabetes Mellitus, Type 2 / genetics* Diabetes Mellitus, Type 2 / physiopathology Disease Models, Animal Fatty Acids, Nonesterified / blood Genetic Predisposition to Disease Insulin / blood Mutation* Obesity / blood Obesity / genetics* Obesity / physiopathology Phenotype Quantitative Trait Loci* Rats Rats, Inbred F344 Rats, Inbred OLETF Rats, Transgenic Receptors, Leptin / genetics* Severity of Illness Index Signal Transduction Triglycerides / blood
Resource
Rats F344.Z-Leprfa/Tj(strainID=390) F344.Cg-Leprfa(D7Rat16-D7Mgh20)/Tj(strainID=391) F344.Cg-Leprfa(D14Rat23-D14Rat12)/Tj(strainID=392)