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The establishment of 3 specified-pathogen-free marmosets (Callithrix jacchus) during the period May 1969 to January 1973 is described. A brief history of the conventional breeding colony from which the animals were derived is given and hysterotomy and hand-rearing techniques are described.
An outbreak of acute respiratory disease was observed in a colony of marmosets (Callithrix jacchus). Parainfluenza Type I (Sendai) virus was isolated from the lungs and from throat swabs of 2 animals which showed clinical signs of disease. A rising titre of serum neutralizing antibody to the virus isolated was detected in several affected animals. Approximately 50% of the colony showed clinical signs of disease, and 3 animals died. The duration of illness ranged from 3 to 16 days.
The systemic administration of steroid hormone (0.400 mg of Dexamethasone every 2 days), during a 28-day period in marmosets (Callithrix jacchus) produced modifications in the evolution of the experimental periodontal traumatism. The observed changes were osteoporosis and reduction of the periodontal fibers in quantity as well as a reduction of repair process, when compared to the control group that only received the action of the trauma from occlusion.
The effects of an antiserum against human kidney renin and of H-142, a peptide inhibitor of human renin, were studied in the primate Callithrix jacchus (common marmoset). In severely volume-depleted (low-salt diet and repetitive injections of furosemide), conscious marmosets, the antiserum reduced blood pressure to the same extent as the converting enzyme inhibitor teprotide (-31 +/- 7 SEM mmHg and -30 +/- 5 mmHg). In mildly volume-depleted (normal salt diet and single injection of furosemide), conscious marmosets, H-142 and teprotide induced a similar fall in blood pressure (-14 +/- 4 mmHg and -15 +/- 2 mmHg). When H-142 was infused after the injection of teprotide, it had no further effect on blood pressure. Conversely, teprotide was ineffective when injected during the infusion of H-142. These results show that in marmosets blood pressure can be lowered by specific inhibitors of human renin. A converting-enzyme inhibitor has similar effects. Hence the renin-angiotensin system appears to contribute significantly to the maintenance of blood pressure in conscious, volume-depleted marmosets.
Anti-Brucella agglutinins were found in 5 of 53 (9.4%) vampire bats Desmodus rotundus, captured in the State of Bahia, Brasil. Two specimens of Diphylla ecaudata were negative. Fifty specimens of the small monkey, Callithrix penicillata, were also negative.
The gross anatomy and the internal structure of the marmoset (Callithrix jacchus) brain are described based on the observations made on the material obtained from 10 adult animals (native name: sagui). 5 brains were used for gross anatomical observations; the other 5 brains, included in toto in celloidin, were cut into serial sections, properly stained and used for comparative studies of the internal structure. Only general descriptions are given considering the brain because, in further papers, it is intended to go on describing in details the nervous system of this small primate, very common in Brazilian jungles and easily domesticated. It shows to be a very good and inexpensive animal for neurophysiological experiments.
The histochemistry of the hepatic parenchymal cells was studied in four Callithrix jacchus. A large amount of glycogen was noted throughout the lobules while the UDPG-GT and the phosphorylases were found unevenly distributed by the hepatic strands with different degrees of reactivity. Near the central vein one of the livers showed PAS-positive nuclear corpuscles that were more conspicuous in the hepatic cells with a larger amount of cytoplasmic glycogen and weaker UDPG-GT and phosphorylase reactivities. G-6PA (in a larger amount) and LDH (in a moderate amount) were found evenly distributed in the hepatic strands. F-1-6PA was seen sometimes with a stronger reactivity at the peripheral part of the lobules. The enzymes of the pentose shunt (G-6PDH, 6-PGDH and NADPH-2-TR) reacted strongly and as a rule evenly distributed near the hepatic lobules. Occasionally they reacted more intensely in the row of hepatic cells disposed just around the central vein. Cytochrome oxidase showed a very faint reaction. Cis-aconitase and ICDH were weak or moderate. NADH-2-TR more than SDH more than MDH were seen frequently diffused near the hepatic strands. SDH and MDH in some instances showed a stronger reactivity in the row or group of hepatic cells around the central vein. ATPase at pH 6.3 was negative in the marmoset liver; ATPase at pH 7.4 was mainly found in the wall of the portal area vessels; ATPase at pH 8.5 showed a stronger reactivity in the cytoplasm of the hepatic cells and ATPase at pH 9.4 was more abundant in the bile capillaries. The reactivity of the lipid metabolism enzymes was moderate with regard to alpha-GPDH or negligible with regard to beta-OHBDH. Acid phosphatase showed a stronger reaction, but almost limited to the Kupffer cells. The hepatic cells showed only a moderate amount of RNA. Some enzymes of the protein metabolism, such as GDH and leucine aminopeptidase showed a stronger reactivity while some others, such as alanyl aminopeptidase and MAO, were seen diffused near the hepatic lobules in a small amount. Enzymes of the mucopolysaccharide metabolism were not found at all (beta-glucuronidase) or showed only a weak reactivity, such as xylitol dehydrogenase.
In vitro transformation of Callithrix jacchus marmoset lymphocytes was achieved with a nasopharyngeal carcinoma (NPC) derived Epstein-Barr virus (EBV) strain, HKLY-28. Two permanent and virus producing lymphoblastoid cell lines, M81 and M72, were obtained. Comparison between the original HKLY-28 line and both M81 and M72 lines showed that passage in the marmosets lymphocytes greatly enhanced viral production and transforming activity of the virus as observed in cottontop derived B95.8 lymphoblastoid line.
Marmoset monkeys are highly susceptible to tumor induction by type C sarcoma viruses and primate lymphotropic herpeviruses. Six experimental models were reviewed, three sarcoma models induced by Rous, feline or simian sarcoma viruses and three models of lymphoproliferative disease induced by Herpevirus saimiri, H. ateles or Epstein-Barr virus. Relative susceptibility of cotton-topped (Saguinus oedipus oedipus), white-lipped (S. nigricollis, S. fuscicollis subspecies) and commone (Callithrix jacchus jacchus) marmosets to the different viruses was compared.
We inoculated common marmosets (Callithrix Jacchus) with Herpesvirus ateles (HVA), Herpesvirus saimiri (HVS), and Epstein-Barr virus (EBV). HVA-induced tumors contained several cell types, including giant cells reminiscent of the Sternberg-Reed cells observed in human Hodgkin's disease. HVS and EBV did not induce tumors, although HVS was present in lymphocytes and elicited a strong antibody response. EBV elicited only a variable antibody response. We feel that more common marmosets should be used to determine if the pathologic and immunologic lesions caused by HVA would be a suitable animal model for Hodgkin's disease and/or other malignant lymphomas of man. Inconsistency in the induction of tumors by EBV and HVS in common marmosets suggets that this species may be a different type of model for human cancer research than the cottontop marmoset, which is the most susceptible animal host for EBV and HVS oncogenesis.
To obtain experimental support for possible milk-borne infection of human T-cell leukemia virus type-I (HTLV-I), short-term-cultured viral antigen-positive lymphocytes obtained from peripheral blood of adult T-cell leukemia lymphoma complex (ATLL) patients were inoculated into the oral cavity of two adult common marmosets (Callithrix jacchus) in amounts comparable to those of HTLV-I-carrying cells fed to a baby in the milk of seropositive mothers. One of the animals seroconverted 2.5 months after the first inoculation. Cultures of peripheral blood mononuclear leukocytes of the marmoset revealed HTLV-I antigen expression in cells, indicating the establishment of oral infection of HTLV-I in an adult marmoset. The cell number deduced to be responsible for the infection was 5.6 X 10(7) cells (used in the first 2 inoculations). The results suggest that the concept of milk-borne infection of HTLV-I from a seropositive mother to her child is plausible.
The uses and advantages of the common marmoset (Callithrix jacchus jacchus) as an animal model for ethological research were examined. It was found that this species had advantages over Old World primates for work on social behavior as a nearer approximation to the group structure occurring in natural conditions could be obtained in the laboratory. The small size of the common marmoset also made it easier to handle and cheaper to maintain. The adult female gave birth at five-month intervals and usually reared twin offspring. This, and the short generation time, made it an ideal model for mother-infant behavioral studies. The common marmoset was also shown to be a useful model for studies of social play, especially for categorizing the changes in playful behavior with age, and the relationship of the patterns seen in play to other behaviors. It was also suggested that it may be an ideal model for experimental studies of play. Other suggested uses included studies of the relationship of food supply and feeding habits to territory size and group structure, and of the advantages to elder offspring of helping to rear younger siblings. As a result of these observations the common marmoset was considered to have great potential as a model for ethological research, both in its natural habitat and in the laboratory.
The general morphology of the external genitalia was examined in 43 common marmosets (Callithrix jacchus) ranging in age from newborn to adult. At birth, the scrotum was a small irregular fold of skin on either side of the caudal aspect of the penis. The testes were not present in the scrotum until 8--11 months of age. The scrotum covered the penis in the adult male, was devoid of fur, was covered by pearly while nodules, and presented a median raphe. In the young female, the pudendal pad closely resembled the scrotum of the male. The vulva was pendulous, and the small vestibular opening was located near its most ventral aspect and closely resembled the preputial opening of the male. In the adult female, the pudendal pad was pendulous, was studded with white nodules, and closely resembled the scrotum of the male. Sex determination by casual observation resulted in numerous errors. Accurate sex determination was based on differences in the preputial and vestibular openings, demonstration of the glans penis in the prepuce, and palpation of the testes in the scrotum or inguinal region.
A self-sustaining colony of common marmosets, Callithrix jacchus, was established for reproductive research. Methods of management were developed to ensure optimal breeding conditions for marmosets in captivity. Studies of the reproductive biology and endocrinology of this species suggest that the common marmoset may be a suitable model for the human in certain aspects of the ovarian cycle, pregnancy, puberty and the hypothalamic and pituitary control of luteinizing hormone secretion. The rapid rate of reproduction of C. jacchus in captivity allows a relatively large colony to be maintained at moderate cost and also makes this species a most suitable laboratory primate for longer term studies of the safety and efficacy of new contraceptive methods.
Reproductive performances of wild-caught and laboratory-born marmosets maintained in a paired-cage system were summarized. Wild-caught, white-lipped (WL) marmosets (Saguinus fuscicollis, S nigricollis) averaged 2.6 live births per pair per yr compared with 1.6 for cotton-topped (CT) marmosets (S oedipus); S fuscicollis illigeri pairs were the best producers. Of first and second generation laboratory-born animals, crossbred or hybrid WL pairs were the best producers; first generation pairs averaged 2.7 live births per pair per yr, comparable to the production of wild-caught WL pairs. In contrast, laboratory-born Sf illigeri pairs produced only 0.8 live births per pair per yr. No significant differences in reproductive performance were observed between first generation outbred vs inbred and between parent-reared vs hand-reared pairs. Based on limited data, the reproductive capabilities of wild-caught and laboratory-born Callithrix jacchus appeared superior to both WL and CT marmosets. Ten examples of marmoset models in biomedical research were discussed briefly.
Earlier studies have noted the unusual placental anatomy of marmosets and the high frequency of biovular, synchorial twinning. The maintenance of a captive colony of Callithrix jacchus has enabled further studies to be made of embryonic development in this species. Thirty-six embryos from seventeen pregnancies were examined in detail and assigned to horizons on the basis of Streeter's classification of external form and internal structure. The specimens represented tha major part of the embryonic period and, with few exceptions, the structural development of the marmoset closely resembled that of the other primates that have been described. Marmoset embryos of a given horizon were consistently shorter than those of man. The timing of morphogenesis in C. jacchus was different from that observed in man and other primates. There was a considerable delay in early embryogenesis in the marmoset, although subsequent to stage XI, development proceeded at approximately the same rate as other primates. The available evidence suggested that this anomaly was not due to delayed implantation or embryonic diapause but to a generally slower rate of early development. The evolution of synchorial twinning is considered as a possible reason for this mode of development.
Interhemispheric connections of visual cortex were studied in owl monkeys, marmosets, and galagos after multiple injections of horseradish peroxidase into one cerebral hemisphere. Areal patterns of connections were revealed in sections of cortex that was flattened and cut parallel to the surface. Results were related to the locations of known visual areas, especially in owl monkeys, in which more visual areas have been established. The connection patterns in owl monkeys and marmosets are very similar, suggesting that the organization of visual cortex differs little in these two New World simians. Galagos have a basically similar pattern, but the connections are more widespread. In all three primates, connections are not restricted to cortex representing the line of decussation of the retina, and even striate cortex has connections displaced from the border. These connections extend up to 2 mm into area 17 in owl monkeys, and they are most extensive in galagos, where they form foci that are coextensive with regions of high cytochrome oxidase activity. Connections are concentrated in the caudal half of area 18, but protrusions of connections cross of the width of the field. The middle temporal visual area (MT) has unevenly distributed connections throughout, with some increase in density along the border. The dorsomedial visual area (DM) of owl monkeys has connections restricted to the rostral border, and a similar region of sparse connections identifies the probable location of DM in marmosets and galagos. Caudal parts of the dorsolateral visual area (DL) of owl monkeys have dense interhemispheric connections. Other visual areas are characterized by unevenly distributed clumps of connections, suggesting that functions are not uniformly distributed, and that semiregular processing modules exist. The results indicate that most extrastriate visual neurons are subject to interhemispheric influences and support the conclusion that callosal connections are functionally heterogeneous.
In the course of characterizing the distribution of putative catecholaminergic neurons in the brain of the common marmoset, we encountered a population of such cells in the basal forebrain. Tyrosine hydroxylase-immunoreactive neurons are abundant within the nucleus basalis magnocellularis throughout its entire rostrocaudal extent, but not in other cholinergic basal forebrain nuclei. Most tyrosine hydroxylase-immunoreactive cells are large and multipolar. Double staining with antibodies to choline acetyltransferase or nerve growth factor receptor confirmed that these tyrosine hydroxylase-immunoreactive neurons are cholinergic, and compose at least 40% of the nucleus basalis cholinergic cells. The presence of a catecholamine-synthesizing enzyme in the neurons that provide the major cholinergic input to the neocortex may have important consequences for cortical function, and may be relevant to the vulnerability of the nucleus basalis in certain neurodegenerative disorders.