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PubMed2002

Immortalisation of ovarian granulosa and Theca cells of the marmoset monkey Calllithrix jacchus.

In view of the increasing need for laboratory primates in biomedical research it is desirable to develop appropriate primate-specific cell culture models that could prevent or significantly reduce the increasing use of primary cultures and experiments with living animals. Follicular granulosa and theca cells are essential for the control of hormone-dependent processes such as the ovarian cycle and pregnancy, but also for the occurrence of hormone-dependent diseases. For this reason it is of great interest to know more about control mechanisms existing in these follicular cell types and the effect of pharmacological or toxicological agents on them. An immortalisation protocol for the two ovarian cell types of the marmoset monkey (Callithrix jacchus) has been developed. All cell lines established so far were examined with regard to the maintenance of known, tissue-specific features (e.g. hormone responsiveness and enzyme expression). The results obtained indicate that it is worth while cloning and characterising the cell lines in more detail so that they could be used after an adequate validation as a defined test system both for basic research as well as for pharmacological or toxicological screening.

Animal Testing Alternatives↗
PubMed2003

Variable dopamine release probability and short-term plasticity between functional domains of the primate striatum.

Release of the neuromodulator dopamine (DA) is critical to the control of locomotion, motivation, and reward. However, the probability of DA release is not well understood. Current understanding of neurotransmitter release probability in the CNS is limited to the conventional synaptic amino acid transmitters (e.g., glutamate and GABA). These fast neurotransmitters are released with a repertoire of probabilities according to synapse type, and these probabilities show activity-dependent plasticity according to synapse use. Synapses for neuromodulators such as DA, however, are designed for signaling that diverges temporally and spatially from that for fast neurotransmitters: DA receptors are exclusively metabotropic and at sites that extend to extrasynaptic locations and neighboring synapses. In this study, the release probability of DA was explored in real time in limbicversus motor-associated functional domains of the striatum of a primate (marmoset; Callithrix jacchus) using fast-scan voltammetry at a carbon-fiber microelectrode. We show that the probability of axonal DA release varies with striatal domain. Furthermore, release probability exhibits a short-term, activity-dependent plasticity that ranges from depression to facilitation in motor-through limbic-associated regions, respectively. Rapid plasticity does not result from metabotropic D2-like DA receptor activation or ionotropic GABA(A) receptor effects but is dependent on Ca2+ availability. These data reveal that rapid dynamics in DA release probability will participate in the transmission of the patterns and frequencies encoded by DA neuron action potential discharge. Furthermore, the regional variation in these features indicates that limbic-versus motor-associated DA neurons are permitted to generate diverse DA signals in response to a given firing pattern.

Animals↗
PubMed2003

Auditory cortical responses elicited in awake primates by random spectrum stimuli.

Contrary to findings in subcortical auditory nuclei, auditory cortex neurons have traditionally been described as spiking only at the onsets of simple sounds such as pure tones or bandpass noise and to acoustic transients in complex sounds. Furthermore, primary auditory cortex (A1) has traditionally been described as mostly tone responsive and the lateral belt area of primates as mostly noise responsive. The present study was designed to unify the study of these two cortical areas using random spectrum stimuli (RSS), a new class of parametric, wideband, stationary acoustic stimuli. We found that 60% of all neurons encountered in A1 and the lateral belt of awake marmoset monkeys (Callithrix jacchus) showed significant changes in firing rates in response to RSS. Of these, 89% showed sustained spiking in response to one or more individual RSS, a substantially greater percentage than would be expected from traditional studies, indicating that RSS are well suited for studying these two cortical areas. When firing rates elicited by RSS were used to construct linear estimates of frequency tuning for these sustained responders, the shape of the estimate function remained relatively constant throughout the stimulus interval and across the stimulus properties of mean sound level, spectral density, and spectral contrast. This finding indicates that frequency tuning computed from RSS reflects a robust estimate of the actual tuning of a neuron. Use of this estimate to predict rate responses to other RSS, however, yielded poor results, implying that auditory cortex neurons integrate information across frequency nonlinearly. No systematic difference in prediction quality between A1 and the lateral belt could be detected.

Acoustic Stimulation↗
PubMed2003

Husbandry, handling, and nutrition for marmosets.

Marmosets, especially Callithrix jacchus, have become an established part of the laboratory animal community. Information on marmoset life history, behavior, and diet acquired from experience with natural and captive habitats has increased, but the early information from workers with colonies, principally those of tamarins, has led to some common perceptions about how to house, handle, and especially, feed callitrichids that may not apply to marmoset requirements. The availability of commercially produced, almost-complete base diet components and a wider variety of cage construction materials, combined with the recent emphasis on the integration of engineering and performance standards for housing, have made captive life and the implementation of research requirements better for the animals and the people that work with them. We will review some of the routine aspects of husbandry, handling, and nutrition for marmoset monkeys maintained in a research setting.

Animal Husbandry↗
PubMed2003

Marmoset models commonly used in biomedical research.

The common marmoset (Callithrix jacchus) is a small, nonendangered New World primate that is native to Brazil and has been used extensively in biomedical research. Historically the common marmoset has been used in neuroscience, reproductive biology, infectious disease, and behavioral research. Recently, the species has been used increasingly in drug development and safety assessment. Advantages relate to size, cost, husbandry, and biosafety issues as well as unique physiologic differences that may be used in model development. Availability and ease of breeding in captivity suggest that they may represent an alternative species to more traditional nonhuman primates. The marmoset models commonly used in biomedical research are presented, with emphasis on those that may provide an alternative to traditional nonhuman primate species.

Animals↗
PubMedDate not supplied

An evaluation of two animal models for dietary influences on reproductive toxicology.

Chronic protein deficiency (8 weeks) was examined in marmosets (Callithrix jacchus) and sub-acute (1 week) methionine- and choline-deprivation was investigated in F344 rats. The marmosets were considered to have become protein-deficient but there was no alteration in sperm morphology, either at the end of the diet or 5 weeks later. Weight loss was also observed in rats on the methionine- and choline-free diet and they had significantly decreased sperm counts 4 weeks after the end of treatment. However, there was no effect on sperm morphology, or on the proportion of cytosine residues that were methylated in the sperm DNA.

Animals↗
PubMed1991

[Wound healing of the cornea of New World monkeys after surface keratectomy: Er:YAG-excimer laser].

Corneal wound healing was studied after photoablation with an excimer laser (193 nm, 43 pulses at 180 mJ/cm2 [symbol: see text] 11 microns ablation depth, optical zone 2.0 mm) and with an erbium-YAG laser (2.94 microns, 5 pulses at 2.5 J/cm2 [symbol: see text] 50 microns ablation depth, optical zone 1.6 mm). The corneas of marmosets (Callithrix jacchus) were prepared 5 and 10 days and 4 and 25 weeks after photoablation. The sections were investigated by conventional light microscopy or exposed to antibodies against collagen types I, III, IV, VII and laminin and stained by indirect immunofluorescence. Macroscopically, the time-course of wound healing was comparable to that seen, after laser keratomileusis for correction of myopia in humans (epithelium closure after 24-48 h, subepithelial haze: erbium-YAG less than or equal to excimer). Histologically the time-course of wound healing could be schematically divided into three phases: (1) epithelial hyperplasia, inhomogeneous new synthesis of collagen fibrils subepithelially; (2) reorganization of the epithelium, hyperplasia of keratocytes, incipient reorganization of the collagen fibrils, increase in subepithelial haze; (3) reorganization of the collagen fibrils, decrease in subepithelial haze. The distribution of collagen type VII during the corneal wound healing suggests that the subepithelial haze observed during the healing process after laser keratomileusis for correction of myopia is based on the anchoring fibrils of the basement membrane.

Animals↗
PubMed1991

CO2 breath tests using 14C-caffeine, 14C-methacetin and 14C-phenacetin for assessing postnatal development of monooxygenase activities in rats and marmosets.

The time course in which the activities of cytochrome P450-dependent drug-metabolizing enzymes develop during the perinatal period differs for various types of monooxygenases as well as for various animal species. Using [3-methyl14C]-, [7-methyl14C]-caffeine, [14CH3]-methacetin and [14C2H5]-phenacetin as substrates in breath tests, the developmental changes in the rates of 14CO2 formation, due to changes in the activity of monooxygenases, were studied in rats and marmoset monkeys (Callithrix jacchus). In rats a rate of 0.006% of the dose administered/min was found to be exhaled as 14CO2 in the caffeine breath tests on the 1st day of life. This value increased gradually reaching adult rates of 14CO2 exhalation after 21 days for [3-methyl14C]-caffeine and after 25 days for [7-methyl14C]-caffeine. In marmosets the rate of 14CO2 exhalation for [3-methyl14C]- and [7-methyl14C]-caffeine was also low at birth and developed gradually reaching adult values of 14CO2 exhalation within 120-200 days. In rats the capacity for dealkylation of methacetin and phenacetin developed much faster compared with caffeine: 9 days postnatally, the exhalation of 14CO2 reached adult values. Offspring of marmosets reached adult values of 14CO2 exhalation at 8 days postnatally when using [14CO2]-methacetin as substrate and at 30 days postnatally using [14C2H5]-phenacetin in the breath test. The results suggest that the monooxygenases for the N-demethylation of caffeine, the O-demethylation of methacetin and the O-deethylation are rather substrate specific in the two species studied. The breath tests used are sensitive methods for assessing the development of different monooxygenases in vivo in rats and marmosets, and they may well (using 13C-labelled substrates) be applicable for studies in children to monitor effects of certain environmental pollutants.

Acetamides↗
PubMed1991

[Yersinia pseudotuberculosis in New World monkeys].

It is reported on four cases of pseudotuberculosis in 2 Saimiri sciureus, 1 Callithrix jacchus/penicillata hybrid and 1 S. oedipus. The animals came from two different groups, one being infected with Y. pseudotuberculosis serotype I, the other with Y. pseudotuberculosis serotype II. All cases showed intestinal infection of thermophile Campylobacter. Remarkable were severe haemorrhagic components and the distinct RHS-proliferation, especially in the mesenteric lymphatic nodes.

Animals↗
PubMed1990

Immunoregulation in the common marmoset, Calithrix jaccus: functional properties of T and B lymphocytes and their response to human interleukins 2 and 4.

Non-human primates have been used to study immune function to a much lesser extent than readily available strains of inbred rodents. Nevertheless, in situations where it might be desirable, but impossible, to study human immune responses in vivo, lower primates could provide an acceptable alternative. In order to extent the knowledge of T- and B-lymphocyte function in lower primates, the common marmoset Callithrix jaccus was used as an experimental model. The functional similarities between this species and humans at the level of T-B co-operation in the antibody response were examined, and xenoreactive T-lymphocyte clones were obtained from marmoset spleen cells using Epstein-Barr virus (EBV)-transformed human B cells as stimulators. These clones could act as helper cells when co-cultured with human B lymphocytes, inducing the secretion of both IgM and IgG. Lymphokine production by mitogen-stimulated marmoset T-cell clones was also examined. Interleukins (IL) 2 and 4 activities were detected in clone supernatants using bioassays and interferon-gamma (IFN-gamma) was detected using a solid-phase ELISA system. However, SDS-PAGE analysis of biosynthetically labelled marmoset and human T-cell clone supernatant proteins revealed major differences between the soluble T-cell products of the two species. The proliferative responses of marmoset T and B cells to recombinant human IL-2 and IL-4 were also examined. Stimulation of [3H]thymidine uptake was detected in both T cell- and anti-IgM-stimulated B-cell cultures with both of the lymphokines. These results suggests that the key components of the antibody response are functionally conserved between lower primates and man and that the common marmoset may be useful as an in vivo model of immune function, particularly with regard to the role of interleukins such as IL-2 and IL-4.

Animals↗
PubMed1990

Transmammary transmission of mesocercariae of Alaria marcianae (Trematoda) in experimentally infected primates.

A lactating primate, Callithrix jacchus, was infected experimentally with 600 mesocercariae of Alaria marcianae 10 days after parturition to determine if she would transmit the mesocercariae to her offspring. Her twin infants were examined 4 wk postinoculation and 16 mesocercariae were found in their tissues. The female was mated again and gave birth to a litter of triplets. She was not given additional mesocercariae. One infant died within hours of birth without suckling and was found negative for any stage of A. marcianae. The other 2 were allowed to nurse for 5 wk, examined and found to be infected with a total of 115 mesocercariae in various tissues, 1 metacercaria in the lungs, and 1 immature and 2 fully formed ovigerous adults in the small intestines. The female was examined at the same time and 246 mesocercariae were recovered. No other stage was found. Histological examination of her mammary glands revealed numerous mesocercariae in the milk-laden alveoli.

Animals↗
PubMed1989

Differences in transneuronal transport of horseradish peroxidase conjugated wheat germ agglutinin in the visual system: marmoset monkey and guinea pig compared.

Conjugates of the lectin wheat germ agglutinin with horseradish peroxidase have been described as effective transneuronal tracers in different neuronal systems of various mammalian species. Here, the failure is described to detect any sign of transneuronal transport of the tracer in the visual system of adult marmoset monkeys (Callithrix jacchus), in spite of heavy anterograde labeling in the primary visual centers after intravitreous injections. In contrast, in the brains of guinea pigs processed by identical technical parameters, transneuronal anterograde labeling was readily recognized in the contralateral striate cortex, thalamic reticular nucleus, and parabigeminal nucleus. Furthermore, transneuronal retrograde labeling of cell bodies was evident in the thalamic reticular and paragibeminal nuclei, and in the striate cortico-geniculate and cortico-collicular cells. The transneuronal labeling of the cell bodies in the guinea pig striate cortex, which has not been demonstrated before, is taken as a measure for the sensitivity of the histological procedures applied. The failure to demonstrate transneuronal labeling in the marmoset monkey, thus, appears to indicate an interspecies difference in the mechanisms of transneuronal transfer of the tracer used. Positive results in other mammalian species such as other rodents, cat, and Old World monkeys, as obtained in this and other laboratories, further support this view.

Animals↗
PubMed1985

Oral infection of a common marmoset with human T-cell leukemia virus type-I (HTLV-I) by inoculating fresh human milk of HTLV-I carrier mothers.

To obtain definitive evidence that milk-borne infection plays a critical role in the endemy or mother-to-child transmission of human T-cell leukemia virus type-I (HTLV-I), we inoculated concentrated fresh human milk cells obtained from HTLV-I carrier mothers into the oral cavity of a common marmoset (Callithrix jacchus). Twenty-eight milk samples were collected (5-10 ml each) from 17 carrier mothers in the first week after delivery. Cells in the milk were centrifuged down and resuspended in 1/10 vol of the milk fluid. The concentrated cell suspensions were successively inoculated into the oral cavity of a common marmoset. The marmoset was found to be seroconverted by indirect immunofluorescence assay at 2.5 months after the first inoculation of the milk (3.5 X 10(8) cells in total), and was later confirmed to be infected with HTLV-I by the detection of viral antigen expression in short-term cultures of its peripheral blood T-lymphocytes. The results strongly support the working hypothesis that milk-borne infection plays a significant role in the mother-to-child transmission of HTLV-I.

Animals↗
PubMed1988

Embryonic signals during the peri-implantation period in primates.

During the peri-implantation period of pregnancy in primates, chorionic gonadotrophin (CG) is the first clear signal of the embryo's presence and viability. In the marmoset (Callithrix jacchus) implantation begins on Day 11-12 after ovulation and CG is secreted by the embryo from this time. The inner cell mass is necessary for the normal secretion of CG by the trophoblast. Implantation can be disrupted both in vivo and in vitro by antisera to the hCG-beta subunit. The secretion of a platelet activating factor by the preimplantation embryo has yet to be confirmed, as has the physiological function of this and other preimplantation signals. Local sampling by perfusion of the corpus luteum allows a direct measurement of the interactions between luteotrophins and luteolysins, as well as a method of screening potential new agents for regulating the function of the corpus luteum.

Animals↗
PubMedDate not supplied

A marmoset model for some New World dermatotropic leishmaniases.

Callithrix penicillata is a good model for dermatotropic strains of some New World Leishmania species (L. mexicana mexicana, L. m. amazonensis, and L. braziliensis guyanensis). Both amastigotes and promastigotes readily infect these primates, with a relative short period of incubation. The developed lesions parallel those found in man, and despite the self healing presented by some marmosets, cell and serum immunological responses are presented. Skin alterations are confined to the site of inoculum, and visceralization is very rarely found. A good response to standard antimonial treatment makes the model useful for preclinical experiments with promising compounds.

Animals↗
PubMed1982

Junin virus infection of Calithrix jacchus: haematological findings.

Haematological changes produced by experimental Junin virus infection of a platyrrhine monkey, Callithrix jacchus were studied. Normocytic and normochromic anaemia appeared after 7 days post infection (p. i.), and increased steadily until day 21 p. i. Reticulocytes and circulating erythroblasts were elevated during the anaemia, reached a peak on day 7 p. i., and disappeared later. Platelets and leukocytes showed a significant decrease from days 14 and 18 p. i., respectively. These alterations could be attributed to the damage of bone marrow and lymphatic tissue.

Animals↗
PubMed1994

Long-term interleukin-6 administration stimulates sustained thrombopoiesis and acute-phase protein synthesis in a small primate--the marmoset.

Interleukin-6 (IL-6) has been ascribed significant roles in both hematopoiesis and the immune response, although its contribution to host defence as a whole is poorly understood. Because short-term IL-6 treatment was previously shown to stimulate megakaryocytopoiesis, we investigated the effect of long-term administration of IL-6 on megakaryocytopoiesis and other systemic parameters in nonhuman primates. We chose a small primate, the marmoset (Callithrix jacchus), which enabled long-term administration at high doses. Recombinant human IL-6 (rhIL-6) administered at doses of up to 1,000 micrograms/kg/d over 4 and 9 weeks caused a sustained twofold to threefold increase of thrombocyte counts, peaking at 4 weeks. Thrombocyte counts declined thereafter, despite continuing IL-6 administration. The number of bone marrow megakaryocytes at 4 and 9 weeks was not increased compared with controls, but the ploidy grade was augmented, suggesting that IL-6 effects are restricted to mature megakaryocytes in vivo. An acute-phase protein response was observed within 24 hours after the first IL-6 administration and reached a maximum after 1 week of IL-6 administration at 25 micrograms/kg. Serum C-reactive protein, haptoglobin, and ceruloplasmin were increased, whereas albumin and transferrin levels declined. The acute-phase protein response was not associated with any morphologic evidence of hepatocellular damage. The increased levels of Ig and soluble IL-2 receptor in the serum levels reflected systemic immunostimulation. There was no evidence of renal mesangioproliferative pathology. Antibodies against rhIL-6 developed within 2 weeks, continuously increasing during the course of the study. High titers of neutralizing antibodies appeared concomitantly with the decrease in platelet counts and decline in acute-phase proteins. Therefore, despite the pleiotropic effects of IL-6 observed in vitro, long-term administration of IL-6 caused a selective and sustained stimulation of thrombopoiesis in marmosets that was only ablated by the appearance of neutralizing antibodies, and high doses were well tolerated in marmosets. A long-term targeting of IL-6 to cells of the megakaryocytic lineage, without evoking general toxicity, confirms the potential therapeutic usefulness of rhIL-6 for the chronic treatment of thrombocytopenic patients.

Acute-Phase Proteins↗
PubMed1995

Density and habitat use of primates at an Atlantic forest reserve of southeastern Brazil.

About 58.3 km of transects were surveyed throughout 21,800 ha of an Atlantic forest reserve of southeastern Brazil, yielding habitat preference data and density estimates for three of the four primate species present. The densities were calculated using the "Fourier Series Estimator" and were 10.5, 2.2 and 1.2 groups/km2 for Callithrix geoffroyi, Cebus apella robustus and Callicebus personatus personatus, respectively. Alouatta fusca fusca although present, was not seen during the survey. C. geoffroyi was spotted predominantly in the low strata of secondary forests while C. a. robustus preferred the higher strata of primary forests. The encounters with C. p. personatus were rarer but the species seems to occur in the middle strata of both primary and secondary forests. Local populations were estimated at 1644, 344 and 181 groups for these three species, respectively. With the exception of A. f. fusca which seems to occur at extremely low numbers, the densities for the other species are within the range of reported values for other species of these genera.

Analysis of Variance↗