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We previously described a family of rhesus monkeys in which three out of six members had a spontaneous hypercholesterolemia related to a decrease in number of low density lipoprotein receptors (LDL-R) (Scanu et al. 1988. J. Lipid Res. 29: 1671-1681). During the current work an additional female normocholesterolemic offspring was generated from the mating of the original dam and sire. Moreover, from the breeding of one of the affected male offspring with six unrelated normocholesterolemic female monkeys, eight offspring were generated of which three were hypercholesterolemic on a cholesterol-free diet and exhibited the same degree of LDL-R deficiency as shown by studies in skin fibroblast cultures. All of the animals studied had levels of plasma lipoproteina protein ranging between 1.0 mg/dl and 57.5 mg/dl that were only weakly correlated with total plasma cholesterol, LDL cholesterol, and apoB. LDL-R deficiency correlated with plasma LDL but not Lpa. A 7 week fat challenge (16.5% lard, 0.64% cholesterol) that raised the plasma LDL levels markedly had no effect on plasma Lpa. Animals with the single band apoa phenotype moving on SDS-PAGE faster than apoB-100 exhibited a tendency for high plasma Lpa levels which, however, varied widely. Wide variations in Lpa levels were also noted with the other apoa phenotypes. Taken together our results demonstrate a successful transmission to second generation animals of the LDL-R deficiency phenotype and provide evidence that this phenotype correlates well with plasma LDL levels but not Lpa. Our data also suggest that the apoa gene is only partially involved in the regulation of the plasma Lpa levels.
Neven et al. (Sun,) studied this question.