Genetic linkage of hyperglycemia, body weight and serum amyloid-P in an intercross between C57BL/6 and C3H apolipoprotein E-deficient mice.
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, logarithm of odds ratio (OR)(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.
Su
Zhiguang
Z
Department of Radiology, University of Virginia, Charlottesville, 22908, USA.
Li
Yuhua
Y
James
Jessica C
JC
Matsumoto
Alan H
AH
Helm
Gregory A
GA
Lusis
Aldons J
AJ
Shi
Weibin
W
D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics / Q000378:metabolism*; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000235:genetics / Q000502:physiology*; D033481:Chromosomes, Mammalian / Q000235:genetics; D003433:Crosses, Genetic; D005260:Female; D005526:Food, Formulated; D008040:Genetic Linkage; D006943:Hyperglycemia / Q000235:genetics* / Q000473:pathology*; D007328:Insulin / Q000097:blood; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019655:Quantitative Trait, Heritable; D000683:Serum Amyloid P-Component / Q000378:metabolism*
D001057:Apolipoproteins E; D001786:Blood Glucose; D007328:Insulin; D000683:Serum Amyloid P-Component