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PubMed1993

Identification of a competitive binding component in vitamin D-resistant New World primate cells with a low affinity but high capacity for 1,25-dihydroxyvitamin D3.

Monkeys in a number of different New World primate genera express a form of compensated target organ resistance to steroid hormones, including 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3]. Characterization of these phenotypes has previously relied upon the study of the 1,25-(OH)2D3-receptor (VDR) interaction in cultured dermal fibroblasts from affected primates. In this report, we show that three of these prototypic phenotypes can be faithfully reproduced in previously established cultured cell lines: B95-8, EBV-transformed B lymphoblasts from the marmoset (Callithrix jacchus), a New World primate with recognized vitamin D resistance; OMK, renal tubular epithelial cells from the owl monkey (Aotus trivergatus), a New World primate with an Old World primate-like VDR phenotype; and MLA144, transformed B lymphoblasts from a gibbon (Hylobates), an Old World primate that expresses the wild-type VDR phenotype. The rank order of specific nuclear uptake and binding of [3H]1,25-(OH)2D3 to the VDR was OMK > or = MLA144 >> B95-8. Despite a 7- to 9-fold difference in cellular VDR content according to ligand binding analyses, there was no discernible difference in the internalization constant Kin for specific cellular uptake of [3H]1,25-(OH)2D3 (0.12-0.26 nM) or in the quantity of VDR detected by immunoblot analysis. We now speculate that the discrepancy in VDR quantitation by binding and immunoblot analysis in the B95-8 New World primate cell line results from the presence of an intracellular, vitamin D metabolite binding moiety in this cell line that competes with the VDR for metabolite binding.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1983

Alteration of blood coagulation and complement system in neotropical primates infected with Junin virus.

The neotropical primate Callithrix jacchus infected with Junin virus presented an acute disease with hematological and neurological manifestations and died 17 to 24 days after infection. This picture is similar to that of human Argentine hemorrhagic fever (AHF). Blood coagulation and complement studies were performed in ten C jacchus animals inoculated with 10(3) TCID50 of Junin virus, the prototype pathogenic XJ strain. Four monkeys were used as normal controls. Infected monkeys and normal controls were bled to death on days 7, 14, 17, and 21. A progressive decrease in the number of platelets was found after day 7 of infection. On day 21, the last monkey had a value of 24,000/microliters. The levels of blood clotting factors did not change until day 17, when a shortened partial thromboplastin time activated with Kaolin (PTTK) (36 sec) and increased factors VIII (192.2%) and VII-X (266.6%) were found. On day 21, the PTTK was prolonged (50.7 sec) and factors II, V, and VIII, were decreased. Thrombin time was found prolonged from day 14 onward. Fibrinogen and fibrin degradation products (FDPs) were increased on days 17 (754 mg/dl and 9.2 microliters/ml) and 21 (457 mg/dl and 29.4 micrograms/ml). No changes in the levels of alpha 2 macroglobulin were observed. Complement hemolytic levels were found to be low on day 7 (58.3 UCH50, increased on day 14 (165.1), and within normal range at the end of infection (107.2). C3 levels showed a similar pattern. The bone marrow was active and hypercellular, and the number and morphology of megakaryocytes were normal in all but one of infected animals. The results of blood clotting suggest a limited activation. The complement system presented a profile of activation followed by a rebound phenomenon. The activation of complement appeared ten days before the alteration of the clotting system was evident.

Animals↗
PubMed1986

Establishment and characterization of a chronic infectious mononucleosislike syndrome in common marmosets.

Epstein-Barr virus (EBV) was inoculated into two species of marmosets. Successful infection was established in the majority of the animals of one species, Callithrix jacchus, as evidenced by the development of high, persistent levels of antibody against virus-specific capsid and early nonstructural proteins. Antibodies also were produced against the major membrane antigen and, in some animals, against EBV nuclear antigen (EBNA) 2 but not against EBNA 1. This is the antibody profile normally noted in individuals with chronic infectious mononucleosis (IM). EBV-induced lymphoproliferation was not seen, and EBV-specific proteins were not detected in the peripheral blood lymphocytes of infected animals. Hence, EBV infection in C. jacchus apparently does not generally include extensive B-cell involvement. However, the marmosets clearly are useful as a model for EBV primary infection and also possibly for chronic IM.

Animals↗
PubMed1986

Therapeutic effect of the antiviral agent ribavirin in Junín virus infection of primates.

In order to assess the effect of the antiviral Ribavirin on the course of Junín virus infection in Callithrix jacchus, seven inoculated monkeys were treated with 15 mg of the drug, twice a day, starting 6 days after infection when all animals were viremic. The three untreated controls showed typical signs of Junín virus infection at 14 days pi and their mean time of death was 18 days. In contrast, no signs of illness were detected in Ribavirin-treated animals until 24 days pi, when marmosets showed signs of neurological involvement: 5 of these animals died (mean day of death: 36) but the two remaining treated monkeys improved and survived infection without sequelae. The comparison of survival rates (0% vs 28%) and the delay of the mean day of death observed indicates that the Ribavirin treatment used has therapeutic effect on Junín virus infection in vivo.

Animals↗
PubMed1987

Protection of Junín virus-infected marmosets by passive administration of immune serum: association with late neurologic signs.

Argentine hemorrhagic fever (Junín virus) is a human viral disease for which immune therapy proves effective, though a late neurologic syndrome is occasionally associated with the treatment. We attempted to determine in the infected marmoset Callithrix jacchus whether immune therapy leads to protection and/or CNS damage. Fifteen C jacchus were inoculated with 10(3) tissue culture infectious dose 50% (TCID50) of the XJ strain of Junín virus. On day 6 post infection (pi), 12 primates were treated with homologous immune serum. Animals were observed daily; and hematologic, serologic, virologic, and histologic studies were performed. All primates, both treated and controls, presented leukopenia, thrombocytopenia, anemia, and weight loss from day 14 pi onward. The three control animals died on days 22, 25, and 32 pi. Among the 12 treated monkeys, 3 died on days 21, 22, and 29. Hematologic values returned to normal during the second month; initial weight was recovered by the fourth month. Three out of the nine survivors showed neurologic alterations of various degrees, with hind-limb paralysis in the most severe case. Among treated monkeys, viremia and viral titers in the lungs, kidney, and lymph nodes were lower than in controls. Neutralizing antibodies were present in high titers in all treated marmosets, except in the one presenting paralysis in which values were minimal and viral persistence was detected in CNS. In conclusion, immune serum treatment of Junín virus-infected marmosets was found to reduce mortality from 100% to 25%. Viremia and viral titers in organs were lowered, and late neurologic signs appeared in 30% of treated survivors.

Animals↗
PubMed1988

Long-term protection against Argentine hemorrhagic fever in Tacaribe virus infected marmosets: virologic and histopathologic findings.

Tacaribe virus may represent a better alternative than attenuated strains of Junin virus (JV) for immunization against Argentine hemorrhagic fever (AHF) because of possible risk of persistent infection of disease associated with live, attenuated strains. Callithrix jacchus marmosets, which suffer 100% mortality if inoculated with the pathogenic XJ strain of JV, were used to evaluate possible Tacaribe virus persistence, subclinical, or long-term disease and the duration of protection against challenge with JV. Histologic studies did not show pathogenic changes due to Tacaribe virus in primates sacrificed from 7 to 480 days postinoculation (pi). No virus was recovered in tissue samples after primary culture or cocultures with sensitive cells. The presence of anti-Tacaribe neutralizing serum antibodies and protection against pathogenic JV were detected up to 480 days after a single dose of Tacaribe virus. However, anti-Junin antibodies were detected only after challenge. In other experiments, protection against JV was evaluated histologically and virologically. Two primates were immunized with Tacaribe virus, challenged with JV, and sacrificed 18 or 21 days later. Subclinical histopathologic findings were associated with recovery of JV only by the sensitive primary culture-coculture techniques. The immunogenicity, degree of protection, and safety of Tacaribe virus indicate its potential as a vaccine against human AHF.

Animals↗
PubMed2005

Poly(ADP-ribose) polymerase-1 activation in a primate model of multiple sclerosis.

Multiple sclerosis (MS) is an immune-mediated disabling neurological disorder involving inflammation, demyelination, axonal damage, and neurodegeneration. Poly(ADP-ribose)polymerase-1 (PARP-1), a nuclear enzyme linked to DNA repair, has been shown to regulate the cellular inflammatory response through interactions with nuclear factor-kappaB. Extensive PARP-1 activation can, by separate mechanisms, also cause cell death. PARP-1 activation in brain occurs in several settings associated with oxidative stress and DNA damage, and PARP-1 inhibition has been shown to attenuate inflammation and improve neuronal survival in these settings. Here we studied the pattern of PARP-1 activation in a nonhuman primate model of MS, marmoset (Callithrix jacchus) experimental allergic encephalomyelitis (EAE). Characteristic of this model is relapsing and remitting focal demyelination typical of human MS. Immunostaining for poly(ADP-ribose), the enzymatic product of PARP-1, showed PARP-1 activation specifically in plaque areas of EAE brains. Robust immunostaining was found in astrocytes surrounding demyelinated EAE plaques and in scattered nearby microglia, oligodendrocytes, and neurons. The immunostaining also suggested PARP-1 activation in occasional endothelial cells surrounded by microglia or infiltrating peripheral blood cells. Given the importance of PARP-1 in both inflammation and cell death processes, these findings suggest that PARP-1 activation may be a significant factor in the pathogenesis of MS.

Animals↗
PubMed2002

Tardive dyskinesia model in the common marmoset.

Thirteen adult common marmosets (Callithrix jacchus) were given once-monthly injections of haloperidol decanoate (5-15 mg/kg i.m.) for one year. Thereafter, drug-free and treatment periods alternated at 3-month intervals. After 2.5 to 14 months, 12 monkeys showed symptoms of tardive dyskinesia (TD), such as periocular and perioral twitchings, tongue protrusions, masticatory movements, and choreic movements in arms and legs. When TD symptoms were evident, the periodic treatment was interrupted and symptoms persisted for at least 5 months after the last haloperidol dose, worsened by injection of the anticholinergic drug biperiden. An injection of nondepot haloperidol (0.12 or 0.25 mg/kg) produced a reduction of TD symptoms. At the end of the study, nondepot haloperidol was injected once a week at two doses (0.12 and 0.25 mg/kg i.m.). A syndrome of excitation with peculiar behavior, interpreted as acute dystonia, was precipitated in all animals. The animals showed sustained retrocollis, climbing upside down, biting the perch, repetitive turnings, and frequent backward movements. The dystonic movements lasted approximately 6 hours and were reduced but not completely extinguished by biperiden (0.1 mg/kg). The TD syndrome registered in marmosets may provide a useful model for screening new antipsychotics for their propensity to induce TD.

Animals↗
PubMed2002

Beginning-of-dose and rebound worsening in MPTP-treated common marmosets treated with levodopa.

A wide range of motor fluctuations develop in Parkinson's disease (PD) patients after prolonged levodopa (L-dopa) treatment, but few experimental models exist in which these can be investigated. We report on motor fluctuations occurring in MPTP-treated common marmosets (Callithrix jacchus) treated repeatedly with L-dopa. All animals showed an improvement in motor function in response to L-dopa, and rapidly developed peak-dose dyskinesia. During the period of L-dopa action, brief periods of immobility were occasionally observed. After acute L-dopa challenge, animals exhibited a worsening of motor function before improvement, and after the beneficial response to L-dopa declined, motor performance showed rebound worsening to below-baseline values. Before L-dopa challenge and during wearing-off and rebound worsening, leg dystonias were observed. Although these findings cannot necessarily be generalized to all MPTP-treated nonhuman primates, they demonstrate that MPTP-treated marmosets show a range of different motor fluctuations analogous to those seen in PD patients chronically treated with L-dopa. Therefore, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated primates can provide a model in which the pathophysiology of treatment complications can be investigated.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1996

An appraisal of the antiparkinsonian activity of piribedil in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated common marmosets.

The D2 dopamine agonist piribedil is not widely used in the treatment of Parkinson's disease because it was thought to be effective mainly on parkinsonian tremor and to produce a high incidence of peripheral side effects, particular nausea. In this study, we used 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated primates to reevaluate the antiparkinsonian ability of piribedil after its oral administration in the presence or absence of domperidone pretreatment. Adult common marmosets (Callithrix jacchus) were treated with the nigral toxin MPTP to induce a parkinsonian syndrome characterised primarily by bradykinesia and other motor deficits. Oral administration of a solution of piribedil [1-(3,4-methylenedioxybenzyl)-4-(2-pyrimidinyl)piperazine] produced a dose-related reversal of all MPTP locomotor and behavioural deficits. However, this effect was short lived and associated with unwanted effects, particular nausea and retching, which clearly hindered locomotion. In contrast, after pretreatment with the peripheral dopamine antagonist domperidone, administration of piribedil did not induce nausea or retching in MPTP-treated marmosets. In these animals, piribedil caused a more marked and longer lasting enhancement of locomotor activity and a further reduction in behavioural deficits than that observed after administration of piribedil alone. In addition, piribedil induced increased vigilance and awareness. These data show that piribedil can reverse akinesia and rigidity in MPTP-treated primates. In addition, they show the drug to be effective without peripheral side effects when used in conjunction with domperidone. These data indicate that piribedil should be an effective monotherapy for Parkinson's disease.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed2006

Monitoring of EAE onset and progression in the common marmoset monkey by sequential high-resolution 3D MRI.

Experimental autoimmune encephalomyelitis (EAE) induced by myelin-oligodendrocyte glycoprotein (MOG) in common marmosets (Callithrix jacchus) is a model for multiple sclerosis. Here, EAE was induced in four common marmosets by 250-300 microg recombinant rat MOG. In addition to a detailed disability scoring, T2- and T1-weighted high-resolution 3D MRI was performed to assess the onset and development of cerebral lesions. The findings were confirmed by histopathology in all animals. Although the animals exhibited a large heterogeneity with regard to onset and localization of lesions and also to disease duration and severity of disability signs, none of the animals revealed any evidence of recovery. A specification of the disability scoring system to account for different aspects of the disease led to a good concurrence of the first MRI-detectable lesion and the onset of central nervous system (CNS) symptoms. The results suggest that MRI monitoring of white matter lesions in conjunction with disability scores that focus on CNS symptoms may be a suitable method to evaluate novel therapeutic interventions even in the presence of pronounced interindividual heterogeneity.

Animals↗
PubMed1993

Alterations in striatal and extrastriatal D-1 and D-2 dopamine receptors in the MPTP-treated common marmoset: an autoradiographic study.

In adult common marmosets (Callithrix jacchus), MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) treatment induced almost total depletion of cells in the substantia nigra pars compacts (SNc) but partial cell loss in the ventral tegmental area (VTA). There was severe depletion of [3H]-mazindol binding to dopamine (DA) uptake sites in the caudate, putamen, and SNc. The loss of [3H]-mazindol binding in the nucleus accumbens (NAc) and olfactory tubercle (OT) was less marked. [3H]-mazindol binding in the body of caudate nucleus showed a small but significant recovery with increasing post-lesion survival times. The specific binding of [3H]-SCH 23390 to D-1 DA receptor sites was increased after MPTP treatment in all subregions of both caudate and putamen but was unaltered in the NAc and OT. Substantia nigra pars reticulata (SNr), frontal cortex, and medial segment of globus pallidus (GPm) all demonstrated moderate levels of [3H]-SCH 23390 binding in control animals, which were unaffected by MPTP treatment. Specific [3H]-spiperone binding to D-2 DA receptor sites was not altered by MPTP treatment in the subregions of caudate-putamen. Moderate levels of [3H]-spiperone binding were observed in control animals in the NAc, OT, SNc, and the lateral segment of globus pallidus (GP1). [3H]-spiperone binding in the SNc and OT was partially decreased in MPTP-treated animals. The changes in specific [3H]-spiperone and [3H]-SCH 23390 binding induced by MPTP-treatment did not alter with post-lesion survival times. These results demonstrate that MPTP treatment causes greater dopaminergic denervation of the caudate-putamen than in NAc/OT. This resulted in an increase in postsynaptic D-1 DA receptor sites in the caudate-putamen but not in the NAc/OT. Also, there appeared to be loss of presynaptic D-2 DA receptor sites in the SNc and OT. In the caudate-putamen, the loss of presynaptic D-2 DA receptor sites may have masked postsynaptic D-2 DA receptor upregulation.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed2001

Nafenopin-, ciprofibroyl-, and palmitoyl-CoA conjugation in vitro: kinetic and molecular characterization of marmoset liver microsomes and expressed MLCL1.

Acyl-CoA conjugation of xenobiotic carboxylic acids is catalyzed by hepatic microsomal long-chain fatty acid CoA ligases (LCL, EC 6.2.1.3). Marmosets (Callithrix jacchus) are considered genetically closer to humans than rodents and are used in pharmacological and toxicological studies. We have demonstrated that marmoset liver microsomes catalyze nafenopin-, ciprofibroyl-, and palmitoyl-CoA conjugation and that only palmitoyl-CoA conjugation is significantly upregulated (1.7-fold, P < 0.02) by a high fat diet. Additionally, the apparent C(50) values for nafenopin-, ciprofibroyl-, and palmitoyl-CoA conjugation of 149.7, 413.4, and 3.4 microM were comparable to those reported for human liver microsomes viz, 213.7, 379.8, and 3.4 microM, respectively. Comparison with human data was enabled by the cloning of a full-length marmoset cDNA (MLCL1) that encoded a 698-amino-acid protein sharing 83% similarity with rat liver acyl-CoA synthetase (ACS1) and 93 and 90% similarity with human liver LCL1 and LCL2, respectively. MLCL1 transiently expressed in COS-7 cells activated nafenopin (C(50) 192.9 microM), ciprofibrate (C(50) 168.7 microM), and palmitic acid (C(50) 4.5 microM) to their respective CoA conjugates. This study also demonstrated that the sigmoidal kinetics observed for nafenopin- and ciprofibroyl-CoA conjugation were not unique to human liver microsomes but were also characteristic of marmoset liver microsomes and recombinant MLCL1. More extensive characterization of the substrate specificity of marmoset LCL isoforms will aid in determining further the suitability of marmosets as a model for human xenobiotic metabolism via acyl-CoA conjugation.

Amino Acid Sequence↗
PubMed1994

Behavioral assessment of the effects of embryonic nigral grafts in marmosets with unilateral 6-OHDA lesions of the nigrostriatal pathway.

Grafts of embryonic nigral tissue were made into the striatum of marmosets (Callithrix jacchus) which had previously received a unilateral 6-hydroxydopamine (6-OHDA) lesion of the nigrostriatal bundle. The grafts comprised injections of cell suspensions prepared from embryonic (74 day) marmoset ventral mesencephalic tissue targeted at multiple striatal sites in the caudate nucleus, the putamen, and the nucleus accumbens on the same side as the initial lesion. A series of behavioral tests was used to assess the monkeys prior to surgery, following the 6-OHDA lesion, and at regular intervals for 6 months after transplantation surgery. Lesioned and grafted (n = 6) or lesion alone (n = 4) monkeys were matched as far as possible with respect to their scores prior to transplantation so that explicit graft-derived recovery could be distinguished from any spontaneous recovery that might occur. Sham-lesioned or unoperated monkeys served as further controls (n = 5). The grafts were functionally effective as measured by a reduction, and in some cases a reversal, of spontaneous, amphetamine- and apomorphine-induced rotation. The reversal of amphetamine-induced rotation correlated with the number of dopaminergic neurons in the grafts visualized by tyrosine hydroxylase immunohistochemistry. Successful use of the hands was restored by the grafts on tasks in which the monkeys reached into tubes to retrieve food. However, functional recovery was not seen on some other behavioral tests. In particular, grafts did not influence ipsilateral biases induced by the lesion, including the position of the head with respect to the rest of the body, hand preference while reaching for food at a conveyor belt, and neglect of contralateral stimuli either at the conveyor belt or of adhesive labels placed around the feet. Indeed, the graft group was impaired compared with the lesion group in the accuracy of reaches at the conveyor belt. Overall, these results indicate that embryonic nigral grafts can yield a partial recovery from the symptoms induced by unilateral nigrostriatal lesions in a primate model of hemiparkinsonism.

Animals↗
PubMed2000

Distribution of calbindin, parvalbumin, and calretinin immunoreactivity in the reticular thalamic nucleus of the marmoset: evidence for a medial leaflet of incertal neurons.

The placement of the reticular thalamic nucleus (RTN) between the dorsal thalamus and the cortex and the inhibitory nature of reticulothalamic projections has led to suggestions that it "gates" the flow of sensory information to the cortex. The New World diurnal monkey, the marmoset, Callithrix jacchus is emerging as an important "model primate" for the study of sensory processing. We have examined the distribution of Nissl-stained somata and calbindin, parvalbumin, and calretinin immunoreactivity in the ventral thalamus for comparison with other species. Cells were labeled using standard immunohistochemistry, ExtraAvidin-HRP, and diaminobenzidine reaction products. The RTN is constituted by a largely homogeneous population of parvalbumin immunoreactive cells with respect to size and orientation. Calbindin and calretinin immunoreactive cells were only found along the medial edge of the RTN adjacent to the external medullary lamina of the dorsal thalamus and laterally near the ventral RTN. These cells were considered to be part of the zona incerta (ZI). The marmoset ZI could be subdivided into dorsal and ventral regions on the basis of its immunoreactivity to calcium binding proteins. Both the ZI and nucleus subthalamicus Luysi contained scattered calbindin and calretinin immunoreactive cells with well-defined dendritic processes. These cells were clearly different to cells in the dorsal thalamus. Parvalbumin immunoreactive cells in RTN, ZI, and subthalamic nucleus were on average larger than neurons positive for the other calcium binding proteins. Future studies reporting the afferent and efferent projections to the RTN must view their results in terms of the close apposition of RTN and ZI somata.

Animals↗
PubMed2000

Comparative aspects of the metabolism and excretion of cortisol in three individual nonhuman primates.

A radiometabolism study is described to provide the first comparative data on the time course, route, and characteristics of excreted [3H]cortisol metabolites in three nonhuman primates: the common marmoset (Callithrix jacchus), the long-tailed macaque (Macacafascicularis), and the chimpanzee (Pan troglodytes). A low dose (40-100 microCi) of 3H-labeled cortisol was administered intravenously to one adult male of each species and the excreta collected over a 5-day period postinjection. The major proportion of radioactivity was excreted in the urine (>80%). Peak radioactivity in urine was recovered within 5.5 h following injection in all three species, while in the feces peak levels of radioactivity were recovered within 26 h postinjection. In all three species, urinary metabolites were primarily excreted as conjugates (61-87%), whereas the percentage of conjugated metabolites in feces was 50% or less. The number and relative abundance of urinary and fecal [3H]cortisol metabolites were determined by reverse-phase high-performance liquid chromatography (HPLC) and immunoreactivity of the radioactivity peaks was assessed by screening HPLC fractions with established cortisol, corticosterone, and 11-oxoetiocholanolone enzyme immunoassays (EIA), the latter being a group-specific assay for measuring 11,17-dioxoandrostanes. HPLC separation of urinary and fecal extracts revealed multiple peaks of radioactivity, several of which were common to all three species. The relative proportion of these peaks, however, differed considerably among species and between urine and feces. HPLC indicated that native cortisol was a major urinary excretory product in the marmoset, while comparatively small amounts were present in the urine of the macaque and chimpanzee. In contrast, in feces, cortisol was only detected in low amounts in the marmoset and was virtually absent in the macaque and chimpanzee. In all three species, one of the major radioactivity peaks showed a retention time comparable to 11-oxoetiocholanolone and high immunoreactivity in the 11-oxoetiocholanolone EIA. The measurement of urinary- and/or fecal-immunoreactive 11,17-dioxoandrostanes is therefore implicated for noninvasive assessment of adrenal function in Old World monkeys, New World monkeys, and great apes.

Animals↗
PubMed1995

Sequence and evolution of the blue cone pigment gene in Old and New World primates.

The sequences of the blue cone photopigments in the talapoin monkey (Miopithecus talapoin), an Old World primate, and in the marmoset (Callithrix jacchus), a New World monkey, are presented. Both genes are composed of 5 exons separated by 4 introns. In this respect, they are identical to the human blue gene, and intron sizes are also similar. Based on the level of amino acid identity, both monkey pigments are members of the S branch of pigments. Alignment of these sequences with the human gene requires the insertion/deletion of two separate codons in exon 1. The silent site divergence between these primate blue genes indicates a separation of the Old and New World primate lineages around 43 million years ago.

Amino Acid Sequence↗
PubMed1998

Suppression of cortisol levels in subordinate female marmosets: reproductive and social contributions.

Socially subordinate female common marmosets (Callithrix jacchus) have markedly lower plasma cortisol levels than dominant females. Subordinate females also undergo hypoestrogenemic anovulation, and estrogen can elevate glucocorticoid levels. Therefore, we previously hypothesized that this cortisol difference is mediated by rank-related differences in reproductive hormones, probably estradiol. To test this possibility, we characterized the effects of the ovarian cycle and ovariectomy on plasma cortisol concentrations. Beginning in the early follicular phase, basal blood samples were collected from seven cycling female marmosets daily for 16 days and at 2- to 3-day intervals for another 16 days. Samples were collected identically from seven anovulatory subordinate females and seven long-term ovariectomized females. Cortisol levels changed reliably across the ovarian cycle, with levels in the mid- to late follicular, peri-ovulatory, and early luteal phases higher than those in the remainder of the cycle. Cortisol levels of cycling females were significantly higher than those of subordinates at all parts of the cycle, but were significantly higher than those of ovariectomized females only during the midcycle elevation. Unexpectedly, subordinates had significantly lower cortisol levels than ovariectomized females, as well as higher estradiol and estrone levels and lower progesterone and luteinizing hormone (LH) levels. These results confirm that circulating cortisol concentrations are modulated by reproductive function in female marmosets but also indicate that low cortisol levels in subordinate females cannot be attributed simply to hypoestrogenemia. Instead, other factors, such as direct effects of social subordination or suppression of LH levels, contribute to suppression of cortisol in subordinates.

Animals↗