Hypercholesterolemia induced by spontaneous oligogenic mutations in rhesus macaques (Macaca mulatta).

BACKGROUND: A rhesus macaque with the fourth highest plasma cholesterol (CH) levels of 501 breeding macaques was identified 22 years ago. Seven offspring with gene mutations causing hypercholesterolemia were obtained. METHODS: Activity of low-density lipoprotein receptor (LDLR), plasma CH levels and mRNA expression levels of LDLR were measured after administration of 0.1% (0.27 mg/kcal) or 0.3% CH. RESULTS: Activity of p. (Cys82Tyr) of LDLR was 71% and 42% in the heterozygotes and a homozygote, respectively. The mRNA expression level of LDLR in the p. (Val241Ile) of membrane-bound transcription factor protease, site 2 (MBTPS2, S2P protein) was 0.83 times lower than normal levels. LDLR mRNA levels were increased for up to 4 weeks by administration of 0.3% CH before suddenly decreasing to 80% of the baseline levels after 6 weeks. CONCLUSION: Oligogenic mutations of p. (Cys82Tyr) in LDLR and p. (Val241Ile) in MBTPS2 (S2P) caused hypercholesterolemia exceeding cardiovascular risk levels under a 0.1% CH diet.

Night Monkey Hybrids Exhibit De Novo Genomic and Karyotypic Alterations: The First Such Case in Primates.

Using molecular chromosomal analyses, we discovered night monkey hybrids produced in captivity from matings between a female Aotus azarae boliviensis (2n = 50) and a male Aotus lemurinus griseimembra (2n = 53). The parents produced seven offspring in total, including one male and six females-a pattern consistent with Haldane's rule. Chromosomal studies were conducted on four of the hybrid offspring. Two of them showed relatively "simple" mixture karyotypes, including different chromosome numbers (2n = 51, 52), which were formed because of a heteromorphic autosome pair in the father (n = 26, 27). The other two hybrid monkeys exhibited de novo genomic and karyotypic alterations. Detailed analysis of the alterations revealed that one individual carried a mixture karyotype of the two parental species and an X chromosome trisomy (53,XXX). The second individual displayed trisomy of chromosome 18 (52,XX,+18) and a reciprocal translocation between autosomes 21 and 23 (52,XX,+18,t(21;23)). Interestingly, the second monkey exhibited mosaicism among blood cells (mos52,XX,+18[87]/52,XX,+18,t(21;23)[85]), but only a single karyotype (52,XX,+18) in skin fibroblast cells. The X- and 18-trisomies were derived from a doubling of the mother's chromosomes in early embryonic cell division, and the reciprocal translocation likely developed in the bone marrow of the offspring, considering that it was observed only in blood cells. Such occurrence of trisomies in hybrid individuals is a unique finding in placental mammals.

Characterization of obesity in Japanese monkeys (Macaca fuscata) in a pedigreed colony.

BACKGROUND: Japanese monkey, Macaca fuscata, is recognized as the monkey species inhabiting the northernmost area in the world, and thus likely to possess unique fat-depositing mechanisms to resist cold weather in winter. We report that obese females are present in the Wakasa group of Japanese monkey reared in an open enclosure of the Primate Research Institute, Kyoto University. METHODS AND RESULTS: Eight of 12 females were categorized as obese, showing percentage body fat of over 22%. The levels of serum leptin (mean +/- SD, 4.9 +/- 2.3 ng/ml) measured in these obese monkeys were significantly higher than those of non-obese peers of the same group (n = 4; 1.2 +/- 0.5 ng/ml) and another Japanese monkey group (Takahama, n = 14; 0.8 +/- 0.25 ng/ml); however, serum levels of adiponectin, insulin, glucose, hemoglobin A1c, and fructosamine did not differ between obese and non-obese monkeys. Few serum lipid parameters such as triglyceride and cholesterol showed lower levels in obese monkeys than their non-obese peers. CONCLUSIONS: These results show that these obese monkeys in the Wakasa group have not developed obesity-related diseases/disorders such as diabetes. In the Wakasa group, the frequency of obese individuals was high in some maternal lineages, suggesting that genetic factors responsible for obesity may have been inherited in these lineages.