Genetic mediation of lipoprotein cholesterol and apoprotein concentrations in the baboon (Papio sp.).

Genetic effects on serum lipoprotein and apoprotein concentrations were investigated using a paternal half-sib design with 79 progeny of 6 sires. Significant differences (P less than 0.05) were observed among sire progeny groups at 4-6 years of age for serum cholesterol, HDL cholesterol and apoA-I concentrations. A sire effect (P less than 0.10) also was observed for VLDL + LDL cholesterol concentrations, but differences were not observed (P greater than 0.10) among sire progeny groups for apoB concentrations. Estimates of heritability were 0.54 for serum cholesterol, 0.32 for VLDL + LDL cholesterol, 0.78 for HDL cholesterol, 0.56 for apoA-I, and 0.20 for apoB concentration. Genetic (rg) and environmental (re) correlations among serum cholesterol, lipoprotein cholesterol, and apoprotein concentrations were positive except for the negative genetic relationships of apoA-I with apoB (rg = -0.74) and with VLDL + LDL cholesterol (rg = -0.30) concentrations. The phenotypic correlation (rp = 0.31) of VLDL + LDL cholesterol with HDL cholesterol was due entirely to the genetic contribution (0.31) since the environmental contribution was zero. The positive genetic relationship (rg = 0.62) of VLDL + LDL cholesterol and HDL cholesterol may be due to biochemical mechanisms controlling cholesterol turnover since the genetic correlations of VLDL + LDL cholesterol and HDL cholesterol with cholesterol turnover rate were both negative (-0.43 and -0.68, respectively). A strong negative genetic correlation (rg = -0.95) was observed between apoA-I and cholesterol turnover, a finding that suggests a close physiologic relationship between these variables.

Relationship of high density lipoprotein cholesterol to cholesterol metabolism in the baboon (Papio sp.).

Genetic effects on serum high density lipoprotein (HDL) cholesterol concentration and several parameters of a two-pool model of cholesterol metabolism were investigated in 79 baboons, the progeny of 6 sires. Significant differences (P less than 0.05) were observed among the sire progeny groups for HDL cholesterol (HDL-C), cholesterol production rate, cholesterol mass of pool A, and the rate constants KA and KAB. Rank correlations (rs) revealed that the sire progeny group means for HDL-C are closely correlated with those for the cholesterol mass of pool A (rs = 0.89), KA (rs = -0.78), and KAB (rs = -0.94). These strong correlations suggest that pool A, KA, and KAB are influenced to a large degree by the same genes that regulate HDL-C concentration. The strong inverse relationship (rs = -0.78) between HDL-C and KA suggests that the differences among these sire progeny groups for HDL-C are due chiefly to those metabolic processes which regulate cholesterol excretion from pool A. This conclusion is consistent with reports that HDL-C is a preferred precursor for bile acid synthesis.

Genetic effects on serum cholesterol concentrations in baboons.

Six male and 134 female adult baboons were assigned to high or low lines on the basis of response of total serum cholesterol concentration to a high cholesterol, high saturated fat diet. Positive assortative mating of these breeders produced 36 high-line and 42 low-line progeny, of which 30 high-line and 39 low-line progeny survived to one year of age. The mean serum cholesterol concentrations of the progeny produced in the two lines were significantly different at all ages from birth to one year. The serum cholesterol levels at birth were not strongly correlated with subsequent levels, but those after 3 weeks were highly correlated with one another. Heritability of total serum cholesterol concentration was estimated by realized heritability, correlation coefficients between parent and progeny values, and by regression coefficients of progeny values on mid-parent value. Estimates of heritability of serum cholesterol level at birth were low, but from 3 weeks to one year of age they ranged from 0.25 to 0.80 and averaged about 0.45. There was a correlated response of HDL and LDL cholesterol levels at one year to selection for total serum cholesterol.

A comparison of the effects of 50 MeVd leads to be neutron and cobalt-60 irradiation of the kidneys of rhesus monkeys.

Twenty rhesus monkeys had one kidney irradiated (after undergoing unilateral nephrectomies) with one of four doses: 960 or 1080 rads of 50 MeVd leads to Be neutrons, or 2350 or 2700 rads of 60Co. Whereas animals treated with the lower dose of neutrons or 60Co are alive with relatively normal renal function, those treated with the higher dose of neutrons died of radiation nephritis. Animals treated with the higher dose of 60Co developed radiation nephritis but survived. The physiological and histopathological changes of radiation nephritis secondary to neutron irradiation are not qualitatively different from those reported for radiation nephritis secondary to photon irradiation.