| For medical practitioners and the general public - Cholesterol Journal Article Catalog. |
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| Gene expression related to cholesterol metabolism in mouse brain during development Hanaka, S., T. Abe, et al. (2000), Brain Dev 22(5): 321-6. Abstract: Although a large amount of cholesterol is known to be needed for brain maturation and differentiation, cholesterol metabolism during these periods remains unclear. To elucidate the developmental regulation of cholesterol metabolism in the brain, we investigated the expression of 3-hydroxy-3-methyglutaryl-coenzyme A (HMG-CoA) reductase (EC 1.1.1.34), low-density-lipoprotein (LDL) receptor and very-low-density-lipoprotein (VLDL)/apolipoprotein E (apo E) receptor (VLDL receptor) using RNase protection assay (RPA) to quantitate mRNA levels in mouse brain, liver and kidney during development. Messenger RNA levels of HMG-CoA reductase in the brain decreased with age, and those levels at -5 (5 days before birth) and 5 days after birth were significantly higher than the control level of adult mice. The period from -5 to 5 days might correspond to stages of active biogenesis of the membranes of brain cells. The mRNA level of HMG-CoA reductase in the liver was also high at -5 days; a finding that correlated with cell proliferation. On the other hand, mRNA levels of the LDL and VLDL receptors in the brain did not change markedly during development. These results suggest that de novo cholesterol biosynthesis in brain cells plays a major role in the supply of cholesterol to the developing brain, rather than the uptake of cholesterol from serum lipoproteins through lipoprotein receptors. |
| Gene linked to faulty cholesterol transport Gura, T. (1999), Science 285(5429): 814-5. |
| Gene polymorphisms affecting HDL-cholesterol levels in the normolipidemic population Miltiadous, G., M. Hatzivassiliou, et al. (2005), Nutr Metab Cardiovasc Dis 15(3): 219-24. Abstract: BACKGROUND AND AIM: HDL-cholesterol (HDL-C) is inversely related to the risk of ischemic heart disease. Many genes are reported to affect HDL-C serum levels in both hyperlipidemic and normolipidemic populations, though the data are controversial. We examined the effect of common gene polymorphisms known to interfere with HDL-C metabolism (apolipoprotein E, cholesterol ester transfer protein and apolipoprotein A-IV gene polymorphisms) on HDL-C plasma levels in normolipidemic subjects. METHODS AND RESULTS: The study population consisted of 200 normolipidemic individuals visiting our clinic for a routine check-up. None of the above gene polymorphisms affected HDL-C levels in our population. However, participants carrying the allele E4 of the apolipoprotein (apo) E gene, the allele B1 of the TaqIB polymorphisms in the cholesterol ester transfer protein (CETP) gene and the allele T of the apoA-IV gene (A to T polymorphism at site 347) (n = 28) had statistically significantly lower HDL-C levels compared to those not carrying the above allele combination (0.99+/-0.33 vs 1.28+/-0.35 mmol/L, p = 0.04). CONCLUSION: In this study, we describe a subgroup of normolipidemic individuals with low HDL-C levels due to genetic variability, and we discuss the underlying possible mechanisms involved. |
| Gene therapy for cholesterol Brown, M. S., J. L. Goldstein, et al. (1994), Nat Genet 7(3): 349-50. |
| Gene therapy for hepatocellular carcinoma using non-viral vectors composed of bis guanidinium-tren-cholesterol and plasmids encoding the tissue inhibitors of metalloproteinases TIMP-2 and TIMP-3 Tran, P. L., J. P. Vigneron, et al. (2003), Cancer Gene Ther 10(6): 435-44. Abstract: Metalloproteinases (MMPs) and their natural inhibitors (TIMPs) contribute to the regulation of tumor microenvironment. Their expressions are deregulated in almost all human cancers. We report a novel approach to gene therapy of hepatocellular carcinoma (HCC), using repeated injections of DNA plasmids encoding the tissue inhibitors of metalloproteinases (TIMPs) TIMP-2 or TIMP-3, and a novel competent formulation of gene transfer based on nontoxic cationic cholesterol derivatives. The new gene delivery system was efficient in demonstrating the antitumor efficiency of TIMP-2 or TIMP-3 in inhibiting tumor growth of human HuH7 HCC cells xenografted into nude mice. We show, for the first time, an in vivo effect of TIMP-3 in delaying HCC tumor growth. No treatment-related toxicity was noted. An inhibition of angiogenesis and tumor necrosis accompanied the inhibitory effects of TIMP-2 or TIMP-3 on tumor expansion and invasion. We also report a bystander effect produced by transfected HuH7 tumor cells mixed with untransfected cells in 1:1 ratio in culture that resulted in killing 98% of cells within 96 h. In addition, the soluble forms of TIMP-2 and TIMP-3 expressed by transfected cells exerted a cytotoxic effect on untransfected HuH7 cell cultures. Taken together, these results demonstrate the potential efficacy of repeated treatment of secreted TIMP-2 and TIMP-3 for the design of nonviral gene therapy for hepatocarcinoma. |
| Gene transfection into fetal sheep airways in utero using guanidinium-cholesterol cationic lipids Luton, D., N. Oudrhiri, et al. (2004), J Gene Med 6(3): 328-36. Abstract: BACKGROUND: Over the last several years, we have developed a novel class of cationic lipids, cholesterol derivatives characterized by polar head groups with guanidinium functions. We have in particular shown that bis(guanidinium)-tren-cholesterol/dioleoylphosphatidylethanolamine (BGTC/DOPE) cationic liposomes can mediate efficient gene transfection into the mouse airways in vivo via direct intratracheal administration or intranasal instillation. As prenatal gene therapy may be necessary for the treatment of a variety of congenital lung diseases, we have explored in the present work the feasibility of BGTC-mediated gene transfection into the respiratory tract of fetal sheep in utero. METHODS: Thus, BGTC/DOPE liposomes were complexed with plasmids expressing the Escherichia coli chloramphenicol acetyltransferase (CAT) reporter gene and the resulting lipoplexes were administered to fetal sheep at 70 days of gestation via surgical replacement of the airway fluid by the transfection mixture followed by tracheal occlusion. The fetal lungs and tracheas were harvested at 72 h and examined for CAT expression and evidence of toxicity. RESULTS: CAT expression was detected in both lung and trachea homogenates, no CAT expression being observed in control fetuses receiving naked plasmid DNA. Immunohistochemical analysis showed that airway epithelial cells and some mesenchymal cells were transfected. Pulmonary histopathology of varied severity was however observed under our transfection conditions and manifested as focal epithelial and mesenchymal lesions. CONCLUSIONS: These results show that BGTC/DOPE liposomes can mediate gene transfection into the fetal sheep airway epithelium. They also invite the development of optimized BGTC-based formulations and administration conditions with a view to future prenatal gene transfer experiments involving therapeutic genes. |
| Gene transfer and hepatic overexpression of the HDL receptor SR-BI reduces atherosclerosis in the cholesterol-fed LDL receptor-deficient mouse Kozarsky, K. F., M. H. Donahee, et al. (2000), Arterioscler Thromb Vasc Biol 20(3): 721-7. Abstract: HDL cholesterol levels in humans are inversely correlated with the risk of atherosclerosis. The class B scavenger receptor type I (SR-BI) is the first molecularly well-defined HDL receptor, and hepatic overexpression of SR-BI in normal mice has been shown to result in decreased plasma HDL cholesterol levels. To determine whether SR-BI overexpression is proatherogenic or is protective against atherosclerosis, LDL receptor-deficient mice were placed on a high-fat/high-cholesterol diet for 2 or 12 weeks to induce atherosclerotic lesions of different stages and then were injected with a recombinant adenovirus encoding murine SR-BI. Transient hepatic overexpression of SR-BI in mice with both early and advanced lesions significantly decreased atherosclerosis. SR-BI expression was associated with markedly decreased HDL cholesterol and either unchanged or only modestly reduced non-HDL cholesterol levels; in all experiments, the mean HDL cholesterol levels were significantly correlated with atherosclerotic lesion size. These data suggest that interventions that promote HDL cholesterol transport and lower plasma HDL cholesterol levels can suppress atherosclerosis, even when initiated after significant lesion development. Thus, stimulation of hepatic SR-BI activity may provide a novel target for therapeutic intervention in atherosclerotic cardiovascular disease. |
| Gene transfer by guanidinium-cholesterol cationic lipids into airway epithelial cells in vitro and in vivo Oudrhiri, N., J. P. Vigneron, et al. (1997), Proc Natl Acad Sci U S A 94(5): 1651-6. Abstract: Synthetic vectors represent an attractive alternative approach to viral vectors for gene transfer, in particular into airway epithelial cells for lung-directed gene therapy for cystic fibrosis. Having recently found that guanidinium-cholesterol cationic lipids are efficient reagents for gene transfer into mammalian cell lines in vitro, we have investigated their use for gene delivery into primary airway epithelial cells in vitro and in vivo. The results obtained indicate that the lipid bis(guanidinium)-tren-cholesterol (BGTC) can be used to transfer a reporter gene into primary human airway epithelial cells in culture. Furthermore, liposomes composed of BGTC and dioleoyl phosphatidylethanolamine (DOPE) are efficient for gene delivery to the mouse airway epithelium in vivo. Transfected cells were detected both in the surface epithelium and in submucosal glands. In addition, the transfection efficiency of BGTC/DOPE liposomes in vivo was quantitatively assessed by using the luciferase reporter gene system. |
| Gene transfer by guanidinium-cholesterol: dioleoylphosphatidyl-ethanolamine liposome-DNA complexes in aerosol Densmore, C. L., T. H. Giddings, et al. (1999), J Gene Med 1(4): 251-64. Abstract: BACKGROUND: A major challenge of gene therapy is the efficient transfer of genes to cell sites where effective transfection can occur. The impact of jet nebulization on DNA structural and functional integrity has been problematic for the aerosol delivery of genes to pulmonary sites and remains a serious concern for this otherwise promising and noninvasive approach. METHODS: This study examined effects of cationic liposome-DNA formulation on both transfection efficiency (in vitro and in vivo) and jet nebulizer stability. The effects of nebulization and sonication on liposome-DNA particle size characteristics were examined. Electron microscopy of promising formulations was performed using several fixation methods. RESULTS: The cationic lipid bis-guanidinium-tren-cholesterol (BGTC), in combination with the neutral co-lipid dioleoylphosphatidylethanolamine (DOPE), was found to have a degree of stability adequate to permit effective gene delivery by the aerosol route. Optimal ratios of lipids and plasmid DNA were identified. Particle size analysis and ultrastructural studies revealed a remarkably homogeneous population of distinctly liposomal structures correlating with the highest levels of transfection efficiency and nebulizer stability. CONCLUSIONS: Optimizing gene delivery vectors for pulmonary aerosol delivery to respiratory sites must take into account factors other than transfection efficiency in vitro. Effects of liposome-DNA formulation on liposomal morphology (i.e. particle size, multilamellar structure) appear to be relevant to stability during aerosolization. These studies have allowed us to identify formulations that hold promise for successful clinical application of aerosol gene delivery. |
| Gene-drug interaction: additive influence of mutant APOA1 and testosterone on plasma HDL-cholesterol Keyhan, G., J. Rosset, et al. (2002), Clin Biochem 35(5): 341-6. Abstract: OBJECTIVES: Factors associated with decreased plasma high-density lipoprotein (HDL) cholesterol concentration, or hypoalphalipoproteinemia, include androgenic steroids and mutations in APOA1, encoding apolipoprotein (apo) A-I, the main structural protein of HDL. However, there is little information regarding the extent of plasma HDL lowering when exogenous testosterone is used in subjects with monogenic low HDL. DESIGN AND METHODS: A man with coronary heart disease (CHD) had been receiving exogenous testosterone post-orchidectomy. He had marked hypoalphalipoproteinemia, which was not responsive to diet or medication. To identify a possible genetic contribution to his biochemical phenotype, we sequenced the LCAT and APOA1 genes. RESULTS: There were no sequence abnormalities in LCAT, but we found that he was a heterozygote for a novel APOA1 mutation in codon 107 (AAG->TGG), which predicted the replacement of lysine by tryptophan (K107W). Serial biochemical measurements over 11 years showed that plasma HDL cholesterol on either intramuscular or oral testosterone was 0.19 +/- 0.06 mmol/L, while plasma HDL cholesterol on transdermal testosterone was significantly higher at 0.52 +/- 0.18 mmol/L (p = 0.015, unpaired t-test). CONCLUSIONS: The findings suggest that the low plasma HDL cholesterol associated with heterozygosity for mutant APOA1 can become extremely depressed during treatment with oral or intramuscular androgens. The findings also suggest that transdermal testosterone may perturb HDL to a lesser extent than other routes of delivery in such patients. |
| Gene-environment interaction in Alzheimer's disease: a potential role for cholesterol Chandra, V. and R. Pandav (1998), Neuroepidemiology 17(5): 225-32. Abstract: Alzheimer's disease is probably a complex disease caused by an interaction of multiple environmental and genetic factors. Genetic defects include 'causative' genes which are rare and a 'susceptibility' gene (sigma4 allele of apolipoprotein E) which is more common in cases. Recent research suggests that environmental factors may interact with a genetic predisposition to modify the risk of Alzheimer's disease. An interaction between serum cholesterol levels and sigma4 genotype is proposed. The evidence for this gene-environment interaction is discussed. |
| Gene-nutrient interactions: dietary behaviour associated with high coronary heart disease risk particularly affects serum LDL cholesterol in apolipoprotein E epsilon4-carrying free-living individuals Loktionov, A., S. Scollen, et al. (2000), Br J Nutr 84(6): 885-90. Abstract: Apolipoprotein E (ApoE) genotype influence on the relationship between dietary risk factors for cardiovascular disease and blood serum lipid levels was investigated in 132 free-living individuals participating in the European Prospective Investigation of Cancer (EPIC) study. All subjects (age 40-69) were clinically healthy and provided information on their usual diet. ApoE genotype and serum lipid concentrations were determined in all subjects. Relationships of intake of dietary constituents with serum lipid levels were compared in different genotype groups. There was a significant correlation between total serum cholesterol and intake of energy derived from total fat (r 0.195; P 0.025) and saturated fat (r 0.174; P 0.046) in the cohort as a whole. However, individuals with the ApoE epsilon3/epsilon4 genotype displayed a much stronger positive correlation between LDL cholesterol level and the percentage of energy derived from intake of saturated fat (r 0.436; P 0.043). There were no significant associations in the groups with epsilon3/epsilon3 or epsilon2/epsilon2 & epsilon2/epsilon3 genotype. A significant positive correlation between alcohol consumption and HDL cholesterol level was present in individuals bearing ApoE epsilon2 allele. These findings support current public health recommendations that saturated fat consumption should be reduced in order to reduce coronary heart disease risk. Total cholesterol concentrations were positively related to saturated fat intake in the cohort as a whole, but elevated LDL cholesterol levels associated with high saturated fat intake can be expected particularly in those individuals who combine a 'risky' dietary behaviour with the presence of the epsilon4 variant of ApoE. |
| Generation of receptor-active, globotriaosyl ceramide/cholesterol lipid 'rafts' in vitro: A new assay to define factors affecting glycosphingolipid receptor activity Nutikka, A. and C. Lingwood (2004), Glycoconj J 20(1): 33-8. Abstract: Purified renal globotriaosyl ceramide (Gb3)/cholesterol mixtures sonicated heated in a Triton-containing buffer placed below a discontinuous sucrose gradient form glycosphingolipid (GSL)-containing dense lipid structures at the 30/5% sucrose interface after centrifugation. Inclusion of fluorescein-labeled verotoxin 1 B subunit (FITC-VT1 B) within the most dense sucrose layer results in the fluorescent labeling of this Gb3-containing raft structure. Alternatively inclusion of I-labeled VT1 fractionation allows quantitation of binding. FITC-VT1 B effectively competes for I-VT1/Gb3 raft binding. This assay will allow the definition of the optimal raft composition for VT1 (or any other ligand) binding. The effect of several potential cellular raft components are reported. Increased cholesterol content increased VT1 binding. Addition of phosphatidylethanolamine had minimal effect while phosphatidylserine was inhibitory. Although inclusion of sphingomyelin increased the Gb3 content of the "raft" reduced VT1 binding was seen. Inclusion of other glycolipids can also be inhibitory. The addition of globotetraosyl ceramide had no effect; however addition of sulfogalactosyl ceramide but not sulfogalactoglycerolipid inhibited VT1/Gb3 raft binding. These results suggest that certain GSLs can disfavor the formation of the appropriate 'raft' structure for ligand binding that this is dependent on both their carbohydrate lipid structure. Such "deceptor" GSLs may provide an as yet unappreciated mechanism for the regulation of cellular GSL receptor activity. This model is an effective tool to approach the dynamics ligand-binding specificity of GSL/cholesterol-containing lipid microdomains. |
| Generation of regulatory oxysterols: 26-hydroxylation of cholesterol by ovarian mitochondria Rennert, H., R. T. Fischer, et al. (1990), Endocrinology 127(2): 738-46. Abstract: De novo synthesis of cholesterol and low-density lipoprotein (LDL) receptor levels are suppressed in the presence of cholesterol. Recent evidence suggests that a cholesterol metabolite (possibly a hydroxysterol), not cholesterol per se, is the effector that inhibits transcription of genes encoding enzymes involved in sterol synthesis and LDL receptors. We found that 26-hydroxycholesterol inhibits human ovarian cell sterol synthesis, and that luteinized human granulosa cells contain 26-hydroxylase messenger RNA (mRNA). We proceeded to characterize the enzyme generating 26-hydroxycholesterol in the rat ovary. Mitochondria derived from ovaries of PMSG-human CG (hCG) primed immature rats (day 3 post-hCG) metabolized 3H cholesterol into 3H26-hydroxycholesterol in the presence of nicotinamide adenine dinucleotide phosphate and aminoglutethimide (100 micrograms/ml), added to inhibit metabolism of sterols by the cholesterol side-chain cleavage system. The identity of the product was confirmed by chromatography in several systems; recrystallization to constant specific activity and mass spectrometry. Negligible 26-hydroxylase activity was detected in other ovarian subcellular fractions. 26-Hydroxycholesterol formation progressed at a linear rate for up to 40 min and was linearly related to mitochondrial protein added to the incubation mixture. 26-Hydroxylase was markedly stimulated (5-fold) by calcium (0.2 mM). Maximal rates of 26-hydroxycholesterol formation observed were 1 pmol/min.mg protein. This activity is substantially lower than cholesterol side-chain cleavage measured in the absence of aminoglutethimide. Ketoconazole (1-100 microM) inhibited 26-hydroxylase in a dose-dependent manner. Pregnenolone (1-1000 microM) and progesterone (1-100 microM) inhibited 26-hydroxylase in a dose-dependent manner, with appreciable inhibitory effects in the 1-10 microM range. We suggest that 26-hydroxycholesterol is an intracrine regulator that controls cellular sterol metabolism. Formation of 26-hydroxcholesterol in ovarian cells may be regulated by steroidogenic activity in such a way as to ensure availability of steroid hormone precursors. When steroidogenesis is active, 26-hydroxylase is inhibited by products of the side-chain cleavage system, allowing increased de novo sterol synthesis and LDL uptake. With reduced steroidogenic activity and less demand for cholesterol, 26-hydroxylase is not blocked, permitting formation of 26-hydroxycholesterol with attendant reduction in sterol synthesis and LDL receptor gene expression. |
| Generation of viable cholesterol-free mice Wechsler, A., A. Brafman, et al. (2003), Science 302(5653): 2087. |
| Genes, HDL cholesterol and risk of coronary artery disease Miettinen, H. E. and K. Kontula (1999), Duodecim 115(8): 869-74. |
| Genetic & cultural determinants of high-density lipoprotein cholesterol & serum triglycerides among Marwaris of Calcutta Majumder, P. P., S. Nayak, et al. (1996), Indian J Med Res 103: 112-9. Abstract: A genetic epidemiological study of serum lipid and lipoprotein levels was conducted among families of Marwaris residents in Calcutta. A total of 210 families, comprising over 100 individuals, were studied. Analyses were performed to estimate the genetic and environmental effects on the determination of high density lipoprotein cholesterol (HDL-C) and serum triglycerides (TG). Familial correlations for HDL-C and TG were estimated: parent-child and sib-sib correlations were found to be significant. Spouse correlations were not significant. Correlations between environments of siblings were significant. Genetic analysis of data on HDL-C and TG performed under a path model, taking genetic transmission and possible environmental associations among family members into account, indicated that lipid and lipoprotein levels adjusted and standardized for age, gender, education, occupation and disease status are primarily determined by genetic factors. The effects of environmental factors were also significant, although in comparison with genetic factors these effects were much smaller. The estimated genetic heritability for HDL-C was approximately 80 per cent, while that for TG was approximately 55 per cent. The genetic effects and environmental effects were not significantly different between adults and children. |
| Genetic alterations of IL-1 receptor antagonist in mice affect plasma cholesterol level and foam cell lesion size Devlin, C. M., G. Kuriakose, et al. (2002), Proc Natl Acad Sci U S A 99(9): 6280-5. Abstract: Inflammatory cytokines have been linked to atherosclerosis by using cell culture models and acute inflammation in animals. The goal of this study was to examine lipoprotein levels and early atherosclerosis in chronic animal models of altered IL-1 physiology by using mice with deficient or excess IL-1 receptor antagonist (IL-1ra). IL-1ra knockout C57BL/6J mice fed a cholesterol/cholate diet for 3 mo had a 3-fold decrease in non-high-density lipoprotein cholesterol and a trend toward increased foam-cell lesion area compared to wild-type littermate controls. IL-1ra transgenic/low-density lipoprotein receptor (LDLR) knockout mice fed a cholesterol-saturated fat diet for 10 wk showed a 40% increase in non-high-density lipoprotein cholesterol, consistent with the IL-1ra knockout data, although there was no change in lesion size. When these IL1-ra overexpressing transgenic mice on the LDLR knockout background were fed a high-cholesterol/high-fat diet containing cholate, however, a statistically significant 40% decrease in lesion area was observed compared to LDLR knockout mice lacking the transgene. By immunohistochemistry, IL-1ra was present in C57BL/6J and LDLR knockout aortae, absent in IL-1ra knockout aortae, and present at high levels in LDLR knockout/IL-1ra transgene aortae. In summary, IL-1ra tended to increase plasma lipoprotein levels and, when fed a cholate-containing diet, decrease foam-cell lesion size. These data demonstrate that in selected models of murine atherosclerosis, chronic IL-1ra depletion or overexpression has potentially important effects on lipoprotein metabolism and foam-cell lesion development. |
| Genetic analysis of a polymorphism in the human apolipoprotein A-I gene promoter: effect on plasma HDL-cholesterol levels Barre, D. E., R. Guerra, et al. (1994), J Lipid Res 35(7): 1292-6. Abstract: Previous studies have indicated that a G to A substitution at position -76 in the gene encoding apolipoprotein A-I (apoA-I) confers increased plasma high density lipoprotein cholesterol (HDL-C). Increased HDL-C may be a direct consequence of the A allele, or may reflect the action of a locus in linkage disequilibrium with the A allele. To elucidate this question, we examined the effect of this polymorphism in a large sample (n = 409) of unrelated Caucasians and their nuclear families (n = 22). To eliminate the confounding effects of hypertriglyceridemia, individuals with triglyceride levels greater than 150 mg/dl were excluded from the study. ApoA-I genotype was determined by polymerase chain reaction (PCR) amplification of genomic DNA and restriction digestion with Msp I. Individuals were grouped by genotype (GG, GA or AA) and mean adjusted HDL levels of the three groups were compared by one-way analysis of variance. Our analysis indicates that HDL-C levels do not vary by genotype, and no gene dosage effect is apparent in men or in women. Analysis of 22 informative Caucasian nuclear families showed no significant difference between individuals with the A allele and their GG siblings. These data suggest that polymorphism at -76 in the apoA-I gene does not directly affect HDL levels. Therefore, the increased HDL-C levels reported in other populations must reflect linkage disequilibrium between the A allele and a putative HDL-raising allele. As we find no evidence for association between the A allele and high HDL levels, this putative allele must occur at a low frequency in the population sampled in this study. |
| Genetic analysis of cholesterol accumulation in inbred mice Schwarz, M., D. L. Davis, et al. (2001), J Lipid Res 42(11): 1812-9. Abstract: Genetic linkage analysis in the laboratory mouse identified chromosomal regions containing genes that contribute to cholesterol accumulation in the liver and plasma. Comparisons between five inbred strains of mice obtained from the Jackson Laboratory (DBA/2, AKR, C57BL/6, SJL, and 129P3) revealed a direct correlation between intestinal cholesterol absorption and susceptibility to diet-induced hypercholesterolemia. This correlation was lost in the F1 generation arising from crosses between high- and low-absorbing strains. Linkage analyses in AKxD recombinant inbred strains and 129xSJL129F1 N2 backcross mice identified four quantitative trait loci (QTL) that influenced Liver cholesterol accumulation (Lcho1-4) and one locus that affected Plasma cholesterol accumulation (Pcho1). These loci map to five chromosomes and, with one exception, are different from the seven QTL identified previously that influence intestinal cholesterol absorption. We conclude that a large number of genes affects the amount of cholesterol absorbed in the small intestine and its accumulation in the liver and plasma of inbred mice. |