Genetic analysis of metabolic defects in the spontaneously hypertensive rat
Language English Country United States Media print
Document type Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.
Grant support
P01 HL 35018
NHLBI NIH HHS - United States
R01 HL 56028
NHLBI NIH HHS - United States
- MeSH
- Cholesterol blood metabolism MeSH
- Glucose analysis metabolism MeSH
- Glucose Tolerance Test MeSH
- Hyperlipidemias genetics MeSH
- Insulin blood metabolism MeSH
- Insulin Resistance genetics MeSH
- Rats MeSH
- Quantitative Trait, Heritable * MeSH
- Disease Models, Animal MeSH
- Glucose Intolerance genetics MeSH
- Rats, Inbred BN MeSH
- Rats, Inbred SHR genetics metabolism MeSH
- Triglycerides blood metabolism MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Male MeSH
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Research Support, U.S. Gov't, P.H.S. MeSH
- Names of Substances
- Cholesterol MeSH
- Glucose MeSH
- Insulin MeSH
- Triglycerides MeSH
Abnormalities in carbohydrate and lipid metabolism are common in patients with essential hypertension and in the spontaneously hypertensive rat (SHR). To identify chromosome regions contributing to this clustering of cardiovascular risk factors in the SHR, we searched for quantitative trait loci (QTL) associated with insulin resistance, glucose intolerance, and dyslipidemia by using the HXB/BXH recombinant inbred (RI) strains. Analysis of variance in RI strains suggested significant effects of genetic factors. A genome screening of the RI strains with more than 700 markers revealed QTL significantly associated with insulin resistance on Chromosomes (Chrs) 3 and 19. The Chr 19 QTL was confirmed by testing a previously derived SHR-19 congenic strain: transfer of a Chr 19 segment delineated by markers D19Rat57 and D19Mit7 from the Brown Norway (BN/Cr) strain onto the genetic background of the SHR/Ola was associated with decreased insulin and glucose concentrations and ameliorated insulin resistance at the tissue level. These findings suggest that closely linked genes on Chr 19, or perhaps even a single gene with pleiotropic effects, influence the clustering of metabolic disturbances in the SHR-BN model.
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