Blood pressure reference intervals for healthy adult chimpanzees (Pan troglodytes).

BACKGROUND: Cardiovascular disease is the primary cause of morbidity and mortality among captive chimpanzees. But there are no clinical definitions of normotension or hypertension in chimpanzees. METHODS: We analyzed 1 year of blood pressure (BP) data from a population of 261 healthy captive adult chimpanzees using a consistent set of criteria to ascertain health. RESULTS: Systolic BP varied by body weight. Diastolic BP varied by age. Median normotension was 126/63 mmHg, with an upper limit of 147/84 mmHg. We defined categories of pre-hypertension (148/85-153/88 mmHg) and hypertension (≥154/89 mmHg). The prevalence of elevated BP was 15%. The relative risk of mortality was 2.60, compared to normotensive animals. CONCLUSIONS: We used contemporary methods from human laboratory medicine to define reliable reference intervals for chimpanzee BP. Results allow accurate diagnosis of hypertension and pre-hypertension, and demonstrate an effect of elevated BP on mortality.

Comparison of biochemical polymorphisms and short tandem repeat (STR) DNA markers for paternity testing in rhesus monkeys (Macaca mulatta).

Genetic markers are indispensable for molecular and statistical genetic research involving nonhuman primates. Genetic markers must be used to ascertain parentage and to confirm the accuracy of pedigrees based solely on housing or demographic records; otherwise, the results of pedigree, linkage, or quantitative genetic analyses may be unreliable. Until recently, most genetic markers used in nonhuman primates were plasma proteins or isozyme polymorphisms, which were required in large numbers, because levels of genetic variation revealed by these markers were rather low. We compared the newer, PCR-amplified short tandem repeat markers (STRs) with a panel of classical biochemical polymorphic markers, for paternity determination among captive-bred rhesus monkeys. The STR markers exhibited an average genetic diversity of 64% and an expected paternity exclusion probability of 0.443. Both of these were greater than the average 54.5% genetic diversity and 0.298 exclusion probability exhibited by the biochemical markers. The STRs were much more efficient than the biochemical markers for parentage determination, since they required only half the amount of genetic typing data to resolve an average paternity case. Thus, the results of applying these two classes of genetic markers in paternity tests were somewhat different than expected on the basis of theoretical exclusion probabilities. These differences were probably due to inbreeding and other genetic differences among breeding colonies. Because they are more informative and provide rapid and efficient genetic data, STRs are now the method of choice for parentage determination and pedigree corroboration among nonhuman primates.

Recent progress in mammalian cloning.

PURPOSE: Our purpose was to review recent progress in the use of nuclear transfer technology to produce genetically identical mammals. METHODS: A literature review was conducted. RESULTS: The reasons for cloning nonhuman mammals are manyfold including commercial, biomedical, and basic research applications. Individual steps in the nuclear transfer process are itemized, along with a detailed description of the specific approaches used in the production of Dolly, NETI, and DITTO. The potential application of nuclear transfer in the treatment of human infertility is also considered, along with bioethical concerns. Finally, insights are provided concerning the future application of cloning technology in rhesus macaques. CONCLUSIONS: The cloning of a lamb (Dolly) from an adult, mammary gland cell coupled with the successful production of rhesus monkeys (NETI and DITTO) by nuclear transfer of embryonic cells marks the beginning of a "Golden Age" in the development and application of somatic cell cloning technology in mammals.

Technical note: chromosomal and mtDNA analysis of Oliver.

Oliver is an African ape whose species identity has been debated in the popular media and by various scientists since the early 1970s. Although decisive morphological data has never been adduced on Oliver, many reports indicated that Oliver was morphologically unusual for a chimpanzee, particularly in his habitual bipedal posture. In addition, his diploid chromosome number was reported to be inconsistent with either human or chimpanzee, but instead intermediate between those species. We performed standard chromosomal studies which demonstrated that Oliver had the diploid number expected for a chimpanzee (2N = 48) and that the banding patterns of his chromosomes were typical for a chimpanzee and different from both humans and bonobos. We also sequenced a 312 bp region of his mitochondrial DNA D-loop region. Results indicated a high sequence homology to the Central African variety of chimpanzee, Pan troglodytes troglodytes. The highest percent homology was observed with a previously characterized specimen from Gabon, strongly suggesting that Oliver originated from this region.

Rhesus monkeys produced by nuclear transfer.

Genetically identical nonhuman primates can provide a powerful animal model for gene therapy and research activities where the physiological parameters directly or indirectly under study are heritable. Here we demonstrate that nuclear transfer is a viable technology for the production of identical rhesus macaques. Oocytes recovered from gonadotropin-treated females were enucleated by aspiration of the first polar body and underlying ooplasm, then activated by cycloheximide exposure. Individual diploid blastomeres, recovered from in vitro-fertilization-produced embryos (either fresh or frozen-thawed) and used as nuclear donors, were injected under the zona pellucida of enucleated (chromosome-free) oocytes and fused by electric pulses. The reconstituted embryos were cocultured on buffalo rat liver cells before cryostorage and transfer to synchronized host mothers. Of the 9 females receiving a total of 29 reconstituted embryos, 3 became pregnant, with two live births resulting, one male and one female. The parentage of both infants was established unequivocally by genotype analysis at 7 highly variable short tandem repeat loci.

Maintenance of genetic variability in a specific pathogen-free breeding colony.

We used 18 genetic loci including blood groups, isozymes, and a serum protein to evaluate our efforts to preserve genetic variability in a specific pathogen-free (SPF) colony of rhesus monkeys. We compared genetic variability in the SPF population to the virally contaminated, non-SPF population from which it was derived. There was no change in the average gene diversity between the SPF and non-SPF populations. However, gene diversity at blood group Q locus increased significantly in the SPF population, while blood group M locus showed an insignificant trend toward decreased gene diversity. Allele frequencies changed significantly at blood group Q locus, although no alleles were lost from the population. We hypothesized that this change was due to extensive overreproduction by a small number of founder males that possessed the initially rare allele, Q1. There was no evidence that this change was associated with genes involved in viral infection.

Effects of chronic blood loss in a marsupial (Monodelphis domestica).

Monodelphis domestica, the gray short-tailed opossum, is used increasingly as an animal model in studies that require repeated blood sampling. Consequently, it is important to establish safe bleeding regimens. We investigated the effects of repeated blood loss on various hematologic values and on different organs in this species. Approximately 2 ml of blood were taken weekly from 20 animals for 13 weeks. The animals were then necropsied; members of an age- and sex-matched control group were bled (2 ml) once and necropsied immediately to obtain baseline data. Ultimately, each animal in the experimental group lost approximately three times its total blood volume. After the first bleeding in the chronically bled group, the red blood cell counts, hemoglobin, and hematocrit values decreased significantly but remained constant thereafter. In another experimental group bled only once, the hematologic values rose to higher than baseline levels after a rest of 2 weeks. Thereafter the values slowly returned to baseline levels. A notable increase in Howell-Jolly bodies occurred in the chronically bled group. Histologically, there was marked erythroid hyperplasia in the bone marrow and extramedullary hematopoiesis in the spleen, but none in the liver. Because there were no obvious detrimental physiologic effects, we conclude that M. domestica is markedly tolerant of chronic blood loss.