Human Molecular Genetics Advance Access published online on April 4, 2006
Human Molecular Genetics, doi:10.1093/hmg/ddl088
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1 Department of Radiology, University of Virginia, Charlottesville, VA 22908, USA; Cardiovascular Research Center, University of Virginia, Charlottesville, VA 22908, USA
* To whom correspondence should be addressed. Dyslipidemia and hyperglycemia are integral components of the metabolic perturbations in type 2 diabetes. Apolipoprotein E-deficient (apoE-/-) mice develop severe hyperlipidemia and significant hyperglycemia when fed a Western diet containing 21% fat (w/w), 0.15% cholesterol, and 19.5% casein. Using an intercross between C57BL/6J (B6) and C3H/HeJ (C3H) apoE-/- mice, we performed quantitative trait locus (QTL) analysis to identify loci contributing to hyperglycemia and associated traits. Fasting plasma levels of glucose, insulin and serum amyloid-P (SAP) and body weight in 234 female F2 mice were measured after being fed the Western diet for 12 weeks. QTL analysis revealed one significant QTL, named Bglu3 (95.8 cM, LOD 4.1), on chromosome 1 and a suggestive QTL on chromosome 9 (38 cM, LOD 2.3) that influenced plasma glucose levels. Bglu3 coincided with loci on distal chromosomal 1 that had a major influence on plasma SAP levels and body weight. Significant correlations between plasma glucose, SAP, and body weight were observed in F2 mice. Thus, these results demonstrate genetic linkages of hyperglycemia and body weight with SAP, a marker of the acute-phase response, in hyperlipidemic apoE-/- mice and suggest a probability for the Sap gene to be a positional candidate of Bglu3.
Received January 3, 2006
Revised March 30, 2006
Accepted March 30, 2006
Article
Genetic linkage of hyperglycemia, body weight, and serum amyloid-P in an intercross between C57BL/6 and C3H apolipoprotein E-deficient mice
Zhiguang Su 1,
Yuhua Li 1,
Jessica C. James 1,
Alan H. Matsumoto 2,
Gregory A. Helm 3,
Aldons J. Lusis 4,
and
Weibin Shi 5 *
2 Department of Radiology, University of Virginia, Charlottesville, VA 22908, USA
3 Department of Neurosurgery, University of Virginia, Charlottesville, VA 22908, USA
4 Departments of Medicine and of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, CA 90095-1679, USA
5 Department of Radiology, University of Virginia, Charlottesville, VA 22908, USA; Cardiovascular Research Center, University of Virginia, Charlottesville, VA 22908, USA; Department of Neurosurgery, University of Virginia, MR4 room 1171, PO Box 801339, Charlottesville, VA 22908, USA
Weibin Shi, E-mail: ws4v{at}virginia.edu
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