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Diet-dependent obesity and hypercholesterolemia in the New Zealand obese mouse: identification of a quantitative trait locus for elevated serum cholesterol on the distal mouse chromosome 5.

Abstract：

AIMS:New Zealand obese (NZO) mice exhibit a polygenic syndrome of obesity, insulin resistance, and hypercholesterolemia that resembles the human metabolic syndrome. This study was performed in order to locate genes responsible for elevated serum cholesterol and to compare their effects under a standard and high fat diet. METHODS:A backcross population of NZO with SJL mice (NZO x F1(SJL x NZO)) was generated. Mice were raised on a normal or high fat diet and were monitored for 22 weeks (body weight, serum cholesterol, and blood glucose). A genome-wide scan was performed by genotyping of approximately 200 polymorphic microsatellite markers by PCR and linkage analysis was performed with the MAPMAKER program. RESULTS:In the genome-wide scan, a single susceptibility locus for hypercholesterolemia (Chol1/NZO, maximum LOD score 14.5 in a combined population of 523 backcross mice) was identified on chromosome 5. Cholesterol levels were significantly elevated in both male and female homozygous carriers of the Chol1/NZO allele. The locus maps 40cM distal of the previously described obesity locus Nob1 in the vicinity of the marker D5Mit244 and in the vicinity of hypercholesterolemia QTL previously identified in the NZB, CAST, and C57BL/6J strains. Chol1/NZO was not associated with elevated body weight, serum insulin, or hyperglycemia. The high fat diet significantly increased serum cholesterol levels, but the fat content of the diet did not alter the absolute effect of Chol1/NZO. CONCLUSIONS:Chol1/NZO is a major susceptibility locus on the distal mouse chromosome 5, which produces gender-independent hypercholesterolemia in NZO mice. The effect of Chol1/NZO was independent of the dietary fat content and was not associated with the other traits of the metabolic syndrome. Thus, it is suggested that the responsible gene might be involved in cholesterol metabolism.

journal_name

Biochem Biophys Res Commun

journal_title

Biochemical and biophysical research communications

authors

Giesen K,Plum L,Kluge R,Ortlepp J,Joost HG

doi

10.1016/s0006-291x(03)00664-8

subject

Has Abstract

pub_date

2003-05-16 00:00:00

pages

812-7

issue

eissn

0006-291X

issn

1090-2104

pii

S0006291X03006648

journal_volume

304

pub_type

杂志文章

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Diet-dependent obesity and hypercholesterolemia in the New Zealand obese mouse: identification of a quantitative trait locus for elevated serum cholesterol on the distal mouse chromosome 5.