Lipoprotein Mutations in Pigs are Associated with Elevated Plasma Cholesterol and Atherosclerosis

A strain of pigs bearing three immunogenetically defined lipoprotein-associated markers (allotypes), designated Lpb5, Lpr1, and Lpu1, has marked hypercholesterolemia on a low fat, cholesterol-free diet. Unlike individuals with familial hypercholesterolemia or WHHL rabbits, the affected pigs have normal low density lipoprotein receptor activity. The animals, by 7 months of age, have extensive atherosclerotic lesions in all three coronary arteries. This strain of pig represents an animal model for atherosclerosis and hypercholesterolemia associated with mutations affecting the structures of plasma lipoproteins. One of the variant apolipoproteins, Lpb5, is apolipoprotein-B. A second variant apolipoprotein (Lpr1), termed apo-R, is a 23-kilodalton protein present in both the very low density (d < 1.006 g/ml) and the very high density (d > 1.21 g/ml) fractions of pig plasma. Isoforms of this protein correlate with two Lpr alleles, Lpr$^{1}$ and Lpr$^{2}$. The Lpr genes segregate independently of the Lpb$^{5}$ and Lpu$^{1}$ alleles. The Lpu1 allotype is a component of low density lipoprotein and is genetically linked to Lpb$^{5}$.