Genetic heterogeneity of lipoproteins in inbred strains of mice: Analysis by gel-permeation chromatography

Abstract

To assess genetic variation of murine lipoprotein profiles, plasma lipoproteins of 11 inbred strains, AKR J , BALB cByJ , C3H HeJ , C57BL 6J , C57BL 6ByJ , C57L J , DBA 1LacJ , 129 J , NZB B1NJ , PL J , and SWR J , were analyzed by gel-permeation chromatography (fast peptide liquid chromatography) and nondenaturing gradient gel electrophoresis. Vena caval blood was drawn after 18 to 20 hours of fasting. Plasma triglyceride and cholesterol concentrations ranged from 12.9 mg/dL ( C57BL 6ByJ ) to 66.9 mg/dL ( C3H HeJ ) and from 54.8 mg/dL ( AKR J ) to 128.5 mg/dL ( NZB B1NJ ), respectively. Mouse strain-related heterogeneities of very low-, low-, and high-density lipoprotein (VLDL, LDL, and HDL, respectively) concentrations were documented; VLDL-triglyceride concentrations ranged from 7.5 mg/dL to 38.8 mg/dL, LDL cholesterol from 12.0 mg/dL to 39.6 mg/dL, and HDL cholesterol from 41.3 mg/dL to 92.4 mg/dL. Hyper-VLDL-triglyceridemia was present in C3H HeJ and SWR J strains and hyper-LDL-cholesterolemia in NZB B1NJ , C3H HeJ , and DBA/1 LacJ. VLDL cholesterol/VLDL triglyceride ratios also ranged widely among strains (0.13 to 0.43), with C57BL 6J , C57BL 6ByJ , and C57L J , the strains particularly susceptible to diet-induced atherosclerosis, having the highest VLDL-lipid ratio. LDL and HDL size heterogeneities were also observed. LDL and HDL diameters ranged between 24.1 nm and 29.4 nm, and between 9.24 nm and 10.32 nm, respectively. Although LDL sizes showed no segregation, HDL sizes fell into two groups. C57L J and C57BL 6J possessed low HDL-cholesterol concentrations and small-sized HDL. HDL sizes were positively correlated with HDL-cholesterol concentrations ( r = .90, P < .001) and LDL-cholesterol concentrations ( r = .85, P < .001), but LDL sizes did not correlate with lipoprotein concentrations. The correlation between HDL sizes and HDL cholesterol concentrations was still significant ( r = .88, P < .003), even if C57L J and C57BL 6ByJ , which are similar to C57BL 6J , were omitted from the analysis. Further studies on the contributions of genetic and dietary factors to the strain-related lipoprotein heterogeneities in inbred strains of mice should prove to be useful for understanding the control of lipoprotein metabolism.