A genetic and correlation analysis of liver cholesterol concentration in rat recombinant inbred strains fed a high cholesterol diet.
Liver cholesterol concentration in rats fed a high cholesterol diet, is under genetic control which is supported by significant differences observed among inbred strains. For instance, the Brown Norway (BN-Lx/Cub) rat developed a twofold higher liver cholesterol concentration than the spontaneously hypertensive rat (SHR/Ola). In the current study, we used 30 recombinant inbred (RI) strains, derived from BN-Lx and SHR progenitors, to locate quantitative trait loci (QTL) that are responsible for differences in liver cholesterol concentrations between the BN-Lx and SHR strains. The heritability of liver cholesterol was estimated to be 0.55 and a significant association was detected between concentration of liver cholesterol and the D10Cebrp1016s2 marker on chromosome 10 (lod score = 3.3); this putative QTL was responsible for nearly 64% of additive genetic variability and thus represents a major genetic determinant of liver cholesterol concentration. Liver cholesterol concentrations significantly correlated with intermediate density lipoprotein (IDL) cholesterol levels.
Bottger
A
A
Department of Laboratory Animal Science, Veterinary Faculty, Utrecht University, The Netherlands.
Lankhorst
E
E
van Lith
H A
HA
van Zutphen
L F
LF
Zídek
V
V
Musilová
A
A
Simáková
M
M
Poledne
R
R
Bílá
V
V
Køen
V
V
Pravenec
M
M
D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D002784:Cholesterol / Q000097:blood / Q000378:metabolism*; D002791:Cholesterol, Dietary / Q000008:administration & dosage*; D002874:Chromosome Mapping; D004036:Diet, Atherogenic; D005260:Female; D008040:Genetic Linkage; D008074:Lipoproteins / Q000097:blood; D008099:Liver / Q000378:metabolism*; D008297:Male; D029363:Organic Anion Transporters, Sodium-Dependent; D010641:Phenotype; D019655:Quantitative Trait, Heritable; D051381:Rats; D011914:Rats, Inbred BN; D011918:Rats, Inbred SHR; D011995:Recombination, Genetic; D013045:Species Specificity; D027981:Symporters
D002352:Carrier Proteins; D002791:Cholesterol, Dietary; D008074:Lipoproteins; D029363:Organic Anion Transporters, Sodium-Dependent; D027981:Symporters; C030104:lipoprotein cholesterol; C071908:sodium-bile acid cotransporter; D002784:Cholesterol