Biochemical and pathological features of a modified strain of Watanabe heritable hyperlipidaemic rabbits

A modified strain of heritable hyperlipidaemic rabbit has been produced by crossing male albino rabbits homozygous for low density lipoprotein receptor deficiency into a coloured commercial colony with strong breeding characteristics. The genetic deficiency has been preserved in the resulting offspring through many generations. Litter numbers, live weight gains and energy intake are similar to normal rabbits. Free and esterified cholesterol in serum, and total cholesterol in very low density plus low density lipoproteins, are markedly increased in homozygote, but only slightly raised in heterozygote, animals. High density lipoprotein-cholesterols show an opposite trend but with less marked differences between the genetic strains. Liver total and esterified cholesterol levels were substantially increased in homozygotes, and the ability of liver membranes to bind human 125I-LDL was markedly reduced, owing to a reduction of the number of high-affinity binding sites. All animals with serum cholesterol values greater than 14 mmol/l at weaning developed extensive aortic atherosclerosis within 16 weeks. The early lesions had the histological appearances of fatty streaks and progressed to complicated disease at 6-12 months. A distinctive pattern of calcific arteriosclerosis, quite different from atherosclerosis, was observed in most aging heterozygote animals and was associated with extensive renal calcium deposition. Corneal arcus developed in some homozygotes but there was no evidence of cerebral atherosclerosis. We conclude that homozygotes of this modified strain can be used for macroscopic studies of the progression of aortic atherosclerosis in the first 4 months after weaning but after this period a combination of macroscopic and microscopic techniques are required. Heterozygotes are unsuitable for studies of this nature.