title: Genetic heterogeneity of plasma lipoproteins in the mouse: control of low density lipoprotein particle sizes by genetic factors.
abstract: In order to assess the genetic control of sizes and concentrations of mouse plasma low density (LDL) and high density lipoproteins (HDL), we used gel permeation fast protein liquid chromatography (FPLC) and nondenaturing gradient polyacrylamide gel electrophoresis to measure the particle sizes of LDL and HDL. Using chromatography we also quantified LDL-cholesterol and HDL-cholesterol concentrations in plasma and used them as indexes of plasma concentrations of the respective particles among 10 inbred strains (AKR/J, BALB/cByJ, C3H/HeJ, C57BL/6J, C57BL/6ByJ, C57L/J, DBA/1LacJ, 129/J, NZB/BINJ, SWR/J) and three sets of recombinant inbred (RI) strains (AKXL/TyJ, BXH/TyJ, CXB/ByJ) of mice. HDL had a dichotomous distribution among the 10 inbred strains. One group had large HDL particle sizes and high HDL-cholesterol concentrations. Another group had smaller HDL particles and lower HDL-cholesterol concentrations, and HDL sizes and HDL-cholesterol concentrations were significantly correlated. In the RI strains, HDL sizes and HDL-cholesterol cholesterol concentrations clearly segregated with one or another of the progenitor strains, and RI strain distributions showed a strong linkage to the apolipoprotein (apo) A-II gene (Apoa-2). In contrast, LDL-cholesterol concentrations and particle sizes on FPLC did not show dichotomous distributions among the 10 inbred strains. In RI strains, the configuration of the LDL FPLC profiles and LDL-cholesterol concentrations did resemble one or another of the progenitors in the majority of cases, but LDLs of several RI strains resembled neither progenitor strain in profile configuration, and LDL-cholesterol concentrations were both greater and smaller than those of progenitor strains. However, LDL particle diameters (as judged by peaks of LDL-cholesterol profiles) did segregate with progenitors in 29/33 (88%) of RI strains suggesting that a major gene may affect LDL size. In attempting to identify a major LDL-size determining gene, we compared apoB gene restriction fragment length polymorphisms (RFLPs) to the distributions of peak LDL sizes in RI strains. Concordance rates of peak LDL sizes to apoB gene polymorphisms were 18/22 (82%) for the EcoRV RFLP, 5/7 (71%) for HindIII RFLP, and 23/29 (79%) for both (range of P values 0.90-0.95). Thus we could not unequivocally implicate the apoB gene in determining the size of LDL particles. In summary, the genetic control of LDL sizes is more complicated than is the case for HDL; however, the differences in LDL size among these strains of mice may be controlled by a major, as yet unidentified, gene.
authors.affiliation: Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO 63110.
authors.forename: S
authors.initials: S
authors.lastname: Jiao
authors.forename: T G
authors.initials: TG
authors.lastname: Cole
authors.forename: R T
authors.initials: RT
authors.lastname: Kitchens
authors.forename: B
authors.initials: B
authors.lastname: Pfleger
authors.forename: G
authors.initials: G
authors.lastname: Schonfeld
mesh_terms: D000818:Animals; D001054:Apolipoproteins A / Q000235:genetics; D001055:Apolipoproteins B / Q000235:genetics; D015153:Blotting, Western; D002850:Chromatography, Gel; D002874:Chromosome Mapping; D004591:Electrophoresis, Polyacrylamide Gel; D008040:Genetic Linkage; D008075:Lipoproteins, HDL / Q000097:blood / Q000235:genetics; D008077:Lipoproteins, LDL / Q000097:blood / Q000235:genetics*; D051379:Mice; D008815:Mice, Inbred Strains; D010316:Particle Size; D012150:Polymorphism, Restriction Fragment Length; D013045:Species Specificity
chemical_list: D001054:Apolipoproteins A; D001055:Apolipoproteins B; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL