Quantitative trait locus mapping of genes that regulate HDL cholesterol in SM/J and NZB/B1NJ inbred mice.
To investigate the quantitative trait loci (QTL) regulating plasma cholesterol, the female progeny of an (SMxNZB/ B1NJ)xNZB/B1NJ backcross were fed an atherogenic diet. After 18 wk, plasma total cholesterol and high-density lipoprotein cholesterol (HDL-C) was measured. HDL-C concentrations were greater in NZB than in SM mice. For standard chow-fed mice, QTL were found near D5Mit370 and D18Mit34. For mice fed an atherogenic diet, a QTL was found near D5Mit239. The QTL for chow-fed and atherogenic-fed mice on chromosome 5 seem to be two different loci. We used a multitrait analysis to rule out pleiotropy in favor of a two-QTL hypothesis. Furthermore, the HDL-C in these strains was induced by the high-fat diet. For inducible HDL-C, one significant locus was found near D15Mit39. The gene for an HDL receptor, Srb1, maps close to the HDL-C QTL at D5Mit370, but the concentrations of Srb1 mRNA and SR-B1 protein and the gene sequence of NZB/B1NJ and SM/J did not support Srb1 as a candidate gene. With these QTL, we have identified chromosomal regions that affect lipoprotein profiles in these strains.
Pitman
Wendy A
WA
The Jackson Laboratory, 600 Main Street, Bar Harbor, Maine 04609, USA.
Korstanje
Ron
R
Churchill
Gary A
GA
Nicodeme
Edwige
E
Albers
John J
JJ
Cheung
Marian C
MC
Staton
Megan A
MA
Sampson
Stephen S
SS
Harris
Stephen
S
Paigen
Beverly
B
D000818:Animals; D002352:Carrier Proteins; D008076:Cholesterol, HDL / Q000097:blood* / Q000737:chemistry; D002874:Chromosome Mapping; D003433:Crosses, Genetic; D018076:DNA, Complementary; D004036:Diet, Atherogenic; D005260:Female; D005838:Genotype; D008075:Lipoproteins, HDL; D008099:Liver / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins; D051379:Mice; D008814:Mice, Inbred NZB; D008815:Mice, Inbred Strains; D010316:Particle Size; D019655:Quantitative Trait, Heritable; D016601:RNA-Binding Proteins; D018110:Receptors, Lipoprotein / Q000235:genetics / Q000378:metabolism; D051122:Scavenger Receptors, Class B
D002352:Carrier Proteins; D008076:Cholesterol, HDL; D018076:DNA, Complementary; D008075:Lipoproteins, HDL; D008565:Membrane Proteins; D016601:RNA-Binding Proteins; D018110:Receptors, Lipoprotein; C454739:Scarb1 protein, mouse; D051122:Scavenger Receptors, Class B; C031616:high density lipoprotein receptors; C075197:high density lipoprotein binding protein