Genetic control of lipid transport in mice. I. Structural properties and polymorphisms of plasma lipoproteins.

To examine genetic factors involved in mammalian lipid transport, we present a detailed analysis of the plasma lipoproteins of the mouse and a survey of these lipoproteins among different inbred strains for genetic variations. Plasma lipoproteins were separated by differential ultracentrifugation into three density fractions: with densities less than 1.006 g/ml, between 1.006 and 1.063 g/ml, and between 1.063 and 1.21 g/ml. On agarose gels, the d less than 1.006 g/ml fraction migrated as a single major band with pre-beta mobility and appeared to correspond to human very low density lipoproteins based on its lipid and protein composition. The intermediate density class was heterogeneous, containing particles with beta and alpha mobilities on agarose gels. The 1.063-1.21 g/ml density fraction exhibited a single alpha-migrating band on agarose gels, characteristic of high density lipoprotein in other mammalian plasma. Marked genetic variation was seen for lipoprotein mobilities among different inbred strains. In Swiss random bred mice, most of the apoprotein was in high density lipoprotein (104 mg/dl of plasma). Lower protein concentrations of 8.5 and 6.2 mg/dl were found in the d = 1.006-1.063 g/ml class and in the very low density lipoprotein, respectively. Proteins thought to be homologous to human apolipoproteins A-I, A-II, B, and E were identified on the basis of their distributions among the lipoprotein fractions, their molecular weights and isoelectric points and, for A-I, B, and E, by their cross-reactivities with antibodies prepared against purified rat apolipoproteins. Considerable structural and quantitative variations also exist among these apolipoproteins isolated from different inbred mouse strains. Our results provide a basis for the use of the mouse as a model system for the study of the genetic control of lipid transport.