Use of monoclonal antibodies in genetic research with nonhuman primates

Monoclonal antibodies, because of their specificity and unlimited availability, have become one of the most powerful experimental tools available to the biological sciences. It is possible to make monoclonal antibodies that bind to determinants that are monomorphic in one or more species or to determinants that are polymorphic within a species. Few monoclonal antibodies have been made using immunogens derived from nonhuman primates. However, some monoclonal antibodies that recognize monotypic markers in humans can be used to detect polymorphic markers in nonhuman primates. Thus, the rapid development of monoclonal antibodies specific for human proteins significantly increases the potential number of immunogenetic markers useful for studying phylogenetic relationships and for identifying genetic polymorphisms among nonhuman primates.     

Genetic management of nonhuman primates

Genetic management is widely recognized as a critical component of the overall management of captive nonhuman primate colonies which produce animals for biomedical research. In this paper, we review the roles of conservation-oriented genetic management, research-oriented genetic management, genetic management at the level of taxomomic class, genetic management at the level of the population, and quantitative genetic analysis in comprehensive genetic management programs for nonhuman primate colonies. We conclude that genetic management is crucial for maintaining nonhuman primate populations suitable for genetic research on normal and disease-related phenotypes. In addition, for research programs that do not have specific genetic objectives, genetic management is essential to facilitate the selection of samples of well-matched unrelated animals for experimental purposes.     

Use of nonhuman primates in cancer research

A short historical review of the use of primates in cancer research is presented followed by a review of various forms of neoplasma observed in the oldest existing Primate Center. Special attention is paid to baboon lymphomas studied for the past two decades at the U.S.S.R. Primate Center at Sukhumi.     

Tumors in nonhuman primates: observations during a six-year period in the Yerkes primate center colony

Tumors were observed in nine of 1,066 nonhuman primates submitted for postmortem examination during a six-year period at the Yerkes Primate Center. Six of these animals had malignant tumors, and one animal had two primary malignancies. Nonhuman primates with tumors included rhesus, squirrel, and pigtail monkeys. Tumors observed included a sarcoma of the stomach, a sarcoma of the thigh, a malignant lymphoma, a glioblastoma of the cerebrum, two renal cell carcinomas, a carcinoma of the endometrium, and three uterine leiomyomas. Two monkeys in the colony presently have malignant tumors, one a testicular seminoma, and the other an abdominal adenocarcinoma, probably of ovarian origin. Electron microscopy revealed virus-like particles in specimens from the thigh sarcoma. The only tumors observed in any of the great ape species during this period have been two surgically removed benign tumors in chimpanzees, a subcutaneous lipoma and a hemangioma of the skin.     

Red cell polymorphisms in nonhuman primates: A review

Abstract: Development as well as current status of the knowledge of nonhuman primate blood groups are discussed together with some practical implications of the red cell antigen polymorphisms in anthropoid apes, Old and New World monkeys and prosimians. Recent data on molecular biology and genetics throw light on the relationships among simian and human red cell antigens and their evolutionary pathways.     

Historical perspective of genetic research with nonhuman primates

Genetics became firmly established as a scientific discipline early in the twentieth century, but major genetic research programs that involve nonhuman primates have been initiated only in the last two decades. Considerable activity in this area has been stimulated by the concurrent development of powerful techniques for detecting variability in chromosomes, proteins, and DNA; the establishment of pedigreed breeding colonies; and the recognition that nonhuman primates are ideally suited as models of human disease and social structure. The subdisciplines of cytogenetics, immunogenetics, and biochemical genetics have established a firm basis for biomedical and evolutionary research with nonhuman primates, and they will contribute greatly to future research initiatives. More recently, the advent of molecular genetics has enhanced the opportunities for research; and the exploration of nonhuman primates as potential models for genetically mediated diseases has been richly rewarded.We stand at the threshold of a new and exciting era in genetic research with nonhuman primates. The results of research programs already underway not only will provide more definitive answers about the origin of man, but also will play a critical role in solving the health-related problems of the present and of the future.     

Implantation of cranial base metallic markers in nonhuman primates.

Cranial base metallic markers are useful in growth and developmental research on the nonhuman primate model. Metallic implants aid in superimposing serial cephalometric roentgenograms in the study of craniofacial changes. They also enable measurement of linear and angular changes in the cranial base. The design of a special implant gun is described in detail. A suggested technique for placement of tantalum markers in the cranial base of nonhuman primates is discussed.     

Viral battery testing in nonhuman primate colony management

Good colony management is associated with monitoring of animals for infectious agents. Of major current concern are B virus and simian AIDS (SAIDS) viruses. However, other viral agents frequently cause serious disease outbreaks which can be avoided if their presence is detected sufficiently early. The recent development of a rapid, sensitive and specific diagnostic test system, i.e., the dot immunobinding assay (DIA) permits the monitoring of a colony for many of the viruses that pose problems. By employing battery type testing using a panel of appropriate viral antigens, investigators are able to detect the increased presence of viral agents of concern and take necessary measures to prevent extension of the problem.     

Designing new microsatellite markers for linkage and population genetic analyses in rhesus macaques and other nonhuman primates

Identification of polymorphic microsatellite loci in nonhuman primates is useful for various biomedical and evolutionary studies of these species. Prior methods for identifying microsatellites in nonhuman primates are inefficient. We describe a new strategy for marker development that uses the available whole genome sequence for rhesus macaques. Fifty-four novel rhesus-derived microsatellites were genotyped in large pedigrees of rhesus monkeys. Linkage analysis was used to place 51 of these loci into the existing rhesus linkage map. In addition, we find that microsatellites identified this way are polymorphic in other Old World monkeys such as baboons. This approach to marker development is more efficient than previous methods and produces polymorphisms with known locations in the rhesus genome assembly. Finally, we propose a nomenclature system that can be used for rhesus-derived microsatellites genotyped in any species or for novel loci derived from the genome sequence of any nonhuman primate.     

Isozymes as bioprobes for genetic analysis of nonhuman primates

The identification and the utilization of genetically determined electrophoretic differences of enzymes between the individuals of species as well as between cell lines have played an important role in the advancement of mammalian genetics during the past quarter of a century. In an explicit search we found a number of red cell enzyme polymorphisms in each of the following four species: chimpanzees, orang utans, rhesus monkeys and brown capuchins. Allelic distribution patterns among populations have indicated trends of subspeciation among chimpanzees and orang utans due to geographic barriers leading to reproductive isolation. Investigations of quantitative levels of red cell glucose-6-phosphate dehydrogenase have suggested that relative activity profiles of certain enzymes among species may be helpful in studies of the evolution of physiological traits and their biological significance during speciation. A large number of biochemical genetic markers in primate-rodent (i.e., chimpanzee-, gorilla-, orang utan-, rhesus monkey- and African green monkey-Chinese hamster) somatic cell hybrids have been identified and are useful for primate genetic analysis. Some of the biologically relevant observations on the enzyme markers in the above mentioned primate species are discussed.     

Bronchoconstriction in nonhuman primates: a species comparison

Bronchoconstriction is a characteristic symptom of various chronic obstructive respiratory diseases such as chronic obstructive pulmonary disease and asthma. Precision-cut lung slices (PCLS) are a suitable ex vivo model to study physiological mechanisms of bronchoconstriction in different species. In the present study, we established an ex vivo model of bronchoconstriction in nonhuman primates (NHPs). PCLS prepared from common marmosets, cynomolgus macaques, rhesus macaques, and anubis baboons were stimulated with increasing concentrations of representative bronchoconstrictors: methacholine, histamine, serotonin, leukotriene D? (LTD?), U46619, and endothelin-1. Alterations in the airway caliber were measured and compared with previously published data from rodents, guinea pigs, and humans. Methacholine induced maximal airway constriction, varying between 74 and 88% in all NHP species, whereas serotonin was ineffective. Histamine induced maximal bronchoconstriction of 77 to 90% in rhesus macaques, cynomolgus macaques, and baboons and a lesser constriction of 53% in marmosets. LTD? was ineffective in marmosets and rhesus macaques but induced a maximum constriction of 44 to 49% in cynomolgus macaques and baboons. U46619 and endothelin-1 caused airway constriction in all NHP species, with maximum constrictions of 65 to 91% and 70 to 81%, respectively. In conclusion, PCLS from NHPs represent a valuable ex vivo model for studying bronchoconstriction. All NHPs respond to mediators relevant to human airway disorders such as methacholine, histamine, U46619, and endothelin-1 and are insensitive to the rodent mast cell product serotonin. Only PCLS from cynomolgus macaques and baboons, however, responded also to leukotrienes, suggesting that among all compared species, these two NHPs resemble the human airway mechanisms best.