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Prion protein immunohistochemical staining in the brains of monkeys with transmissible spongiform encephalopathy.

Prion protein (PrP) immunohistochemical staining of the brains of common marmosets (Callithrix jacchus) with experimental transmissible spongiform encephalopathy is described. The monkeys (n = 17) had been injected, intracerebrally, 17-49 months previously with homogenates of brain tissue taken post mortem from a cow with BSE (n = 2 monkeys), a sheep with natural scrapie (n = 2 monkeys), human cases of growth hormone related Creutzfeldt-Jakob disease (CJD) (n = 2 monkeys), sporadic CJD (n = 5 monkeys), or Gerstmann-Sträussler-Scheinker disease (GSS) (n = 4 monkeys), or from monkeys with spongiform encephalopathy resulting from injection with brain tissue from these last two cases (n = 1 monkey from each case). Only diffuse PrP-staining was seen in monkeys injected with CJD-material whereas more aggregated deposits of PrP were seen in monkeys injected with BSE-, scrapie--and GSS-brain tissue. There were no patterns of staining specific to the brains injected with BSE-material that could be used to identify the origin of that inoculum. BSE--and scrapie-injected monkey brains could be distinguished from each other because in BSE-injected monkey brain the spongiform vacuolation was largely confined to subcortical structures whereas in scrapie-injected monkey brain the spongiform vacuolation was also prominent in the neocortex. The patterns of PrP deposition differed markedly between those seen in monkey brains injected with BSE-material or CJD-material, but the patterns of PrP staining seen in monkey brains injected with BSE-material were also seen in monkey brains injected with scrapie--or GSS-material. Overall there was a correlation between the length of the incubation period and the amount of aggregated PrP-staining, but no correlation between the neuropathological picture and the clinical presentation of neurological signs.

Adult↗

Morphological characteristics of C1 and C2 adrenergic neurone groups in marmoset monkey brainstem by using antibody against phenylethanolamine-N-methyltransferase.

This work describes a mapping study of phenylethanolamine-N-methyltransferase (PNMT) immunoreactive neurones and fibres in the medulla oblongata of the marmoset monkey, Callithrix jacchus. Two groups of PNMT-immunoreactive neurones were found in the marmoset monkey medulla oblongata: a ventrolateral (C1 group) and a dorsomedial PNMT-immunoreactive cells group (C2 group). The PNMT-immunoreactive cells in the ventrolateral group C1 were found to be located around the lateral reticular nucleus. The PNMT-immunoreactive somata within the ventrolateral medulla are round to oval, and mostly multipolar with branched processes. In the dorsomedial group C2, PNMT-immunoreactive cell bodies appeared near the obex. The majority of the dorsomedial PNMT-immunoreactive neurones were observed in the nucleus tractus solitarius; although some were present in the dorsal motor nucleus of the vagus. The PNMT-immunoreactive somata in the dorsomedial medulla were small and round or ovoid. These results provide information upon the adrenergic system in the medulla oblongata of a species that presents a useful model of a small primate brain, the marmoset monkey.

Adrenergic Fibers↗

In vitro development of marmoset monkey oocytes by pre-antral follicle culture.

A technique for in vitro maturation of oocytes from small ovarian follicles of marmoset monkeys (Callithrix jacchus) has been developed. We employed a two-step culture system for primary follicles (45-85 microm) and a one-step culture technique for secondary follicles (>85 microm). The two-step technique started with the culture of stromal tissue fragments for 2 days. Thereafter, mechanically isolated follicles were transferred to a culture system where they attached to the culture surface and grew for up to a further 12 days. Significant growth of the small follicles and their oocytes was only achieved with gonadotrophins in the medium. Oocytes with a mean diameter of 39 microm from follicles <85 microm reached a mean diameter of 90 microm by the end of the two-step culture. After in vitro maturation, 19% of oocytes from these follicles had progressed to the germinal vesicle breakdown (GVBD). Follicles between 85 and 170 microm in diameter were isolated from the stroma and placed directly in the culture. Oocytes from these follicles had a mean diameter of 64 microm. The maximum size the oocytes reached in culture was related to the age of the females (pre-pubertal females: 102 +/- 1.3 microm; adults: 96 +/- 1.4 microm). Twenty-seven per cent of oocytes from pre-pubertal ovaries achieved GVBD and nearly two-thirds of these progressed to polar body stage. From adult ovaries, only 12% progressed to GVBD and one-third of these to polar body stage. It is possible to develop mature oocytes in vitro from marmoset secondary pre-antral follicles (>85 microm). From primary follicles, although near full size oocytes were developed, maturation capacity was incomplete.

Age Factors↗

The effect of a unilateral costochondral graft on the growth of the marmoset mandible.

PURPOSE: The purpose of the investigation was to examine growth of the mandible after costochondral grafting with special reference to the amount of cartilage included in the grafts. MATERIALS AND METHODS: The material consisted of 5 growing and 3 adult marmoset monkeys, Callithrix jacchus, in which the condylar process was removed unilaterally and replaced with a costochondral graft (CCG) containing either a short or long cartilage end. Growing animals were followed for 15 months until they attained maturity; and adult animals were followed for 13 months. Measurements made on frontal radiographs performed bimonthly, and direct measurements made on dry mandibles and crania at the end of the experiment, were used to evaluate the growth of the mandible and glenoid fossa. RESULTS: Longitudinal cephalometric evaluation revealed a gradual deviation of the lower dental midline to the unoperated side in growing monkeys with a long cartilage transplant. In all other animals, virtually no midline deviation occurred. Measurements on dry mandibles showed that the length and ramus height were longer in growing animals with long cartilage transplants compared with those with short cartilage transplants. In adult animals, the amount of cartilage did not make any difference with regard to the mandibular measurements. Enlargement of the articulating head on the grafted side was recorded in all animals. A morphologic change in the glenoid fossa of growing monkeys with a long cartilage transplant was also noted. CONCLUSIONS: The findings of this investigation indicate that depending on the amount of cartilage in a unilateral CCG, a tissue-separating force is generated in growing monkeys, capable of propelling the mandible to the unoperated side. This gradual overgrowth occurs during the entire growth period, indicating a strong hormonal and growth factor influence on the growth process. Jaw function may have an effect on the articulating surface of the CCG, seen as enlarged articulating head on the grafted side in all animals.

Adaptation, Physiological↗

The carboxyterminal peptide of chorionic gonadotropin facilitates activation of the marmoset LH receptor.

Luteinizing hormone (LH) and chorionic gonadotropin (CG) are heterodimeric glycoprotein hormones acting on the luteinizing hormone receptor (LHR). In the LHR, which is genomically encoded by eleven exons, exon 10 encodes for the hinge region and its elimination impairs LH action, while CG maintains normal activity. The two gonadotropins differ in the carboxyterminal peptide (CTP) present in CG but absent in LH. Since the marmoset monkey (Callithrix jacchus) LHR naturally lacks exon 10 (LHR type II), we generated two recombinant marmoset gonadotropin preparations, one consisting of the wild type CG and one of truncated CG lacking the CTP (CG (-CTP)). After calibration in a mouse Leydig cell bioassay against the WHO LH80/522 standard, the ED (50) of the CG preparation on a COS7 cell line permanently expressing the marmoset LHR was 4.25 +/- 0.21 IU/L (n = 3). Stimulation of the COS7 cell line with equipotent concentrations of CG and CG (-CTP) resulted in significantly different formation of cAMP (two-way ANOVA, p < 0.001). In particular, cAMP production stimulated by CG (-CTP) was 3 - 4 times lower compared to CG at the saturating CG concentration (8 IU/L). We conclude, supplementing one current model of LHR activation, that exon 10 might play a permissive role in releasing the constraint of the receptor upon hormone binding, resulting in receptor activation. We speculate that, when exon 10 is lacking, the CTP can overcome its absence and facilitates the opening of the receptor, resulting in normal activation.

Amino Acid Sequence↗

A continuous smooth map of space in the primary visual cortex of the common marmoset.

We examined the fine-scale mapping of the visual world within the primary visual cortex of the marmoset monkey (Callithrix jacchus) using differential optical imaging. We stimulated two sets of complementary stripe-like locations in turn, subtracting them to generate the cortical representations of continuous bands of visual space. Rotating this stimulus configuration makes it possible to map different spatial axes within the primary visual cortex. In a similar manner, shifting the stimulated locations between trials makes it possible to map retinotopy at an even finer scale. Using these methods we found no evidence of any local anisotropies or distortions in the cortical representation of visual space. This is despite the fact that orientation preference is mapped in a discontinuous manner across the surface of marmoset V1. Overall, our results indicate that space is mapped in a continuous and smooth manner in the primary visual cortex of the common marmoset.

Animals↗

Prevention of autoimmune demyelination in non-human primates by a cAMP-specific phosphodiesterase inhibitor.

Experimental allergic encephalomyelitis (EAE) is an autoimmune disease of the central nervous system that serves as a model for the human disease multiple sclerosis. We evaluated rolipram, a type IV phosphodiesterase inhibitor, for its efficacy in preventing EAE in the common marmoset Callithrix jacchus. In a blinded experimental design, clinical signs of EAE developed within 17 days of immunization with human white matter in two placebo-treated animals but in none of three monkeys that received rolipram (10 mg/kg s.c. every other day) beginning 1 week after immunization. In controls, signs of EAE were associated with development of cerebrospinal fluid pleocytosis and cerebral MRI abnormalities. In the treatment group, there was sustained protection from clinical EAE, transient cerebrospinal fluid pleocytosis in only one of three animals, no MRI abnormality, and marked reduction in histopathologic findings. Rolipram-treated and control animals equally developed circulating antibodies to myelin basic protein. Thus, inhibition of type IV phosphodiesterase, initiated after sensitization to central nervous system antigens, protected against autoimmune demyelinating disease.

3',5'-Cyclic-AMP Phosphodiesterases↗

The common marmoset: a new world primate species with limited Mhc class II variability.

The common marmoset (Callithrix jacchus) is a New World primate species that is highly susceptible to fatal infections caused by various strains of bacteria. We present here a first step in the molecular characterization of the common marmoset's Mhc class II genes by nucleotide sequence analysis of the polymorphic exon 2 segments. For this study, genetic material was obtained from animals bred in captivity as well as in the wild. The results demonstrate that the common marmoset has, like other primates, apparently functional Mhc-DR and -DQ regions, but the Mhc-DP region has been inactivated. At the -DR and -DQ loci, only a limited number of lineages were detected. On the basis of the number of alleles found, the -DQA and -B loci appear to be oligomorphic, whereas only a moderate degree of polymorphism was observed for two of three Mhc-DRB loci. The contact residues in the peptide-binding site of the Caja-DRB1*03 lineage members are highly conserved, whereas the -DRB*W16 lineage members show more divergence in that respect. The latter locus encodes five oligomorphic lineages whose members are not observed in any other primate species studied, suggesting rapid evolution, as illustrated by frequent exchange of polymorphic motifs. All common marmosets tested were found to share one monomorphic type of Caja-DRB*W12 allele probably encoded by a separate locus. Common marmosets apparently lack haplotype polymorphism because the number of Caja-DRB loci present per haplotype appears to be constant. Despite this, however, an unexpectedly high number of allelic combinations are observed at the haplotypic level, suggesting that Caja-DRB alleles are exchanged frequently between chromosomes by recombination, promoting an optimal distribution of limited Mhc polymorphisms among individuals of a given population. This peculiar genetic make up, in combination with the limited variability of the major histocompatability complex class II repertoire, may contribute to the common marmoset's susceptibility to particular bacterial infections.

Alleles↗

Proliferation of granule cell precursors in the dentate gyrus of adult monkeys is diminished by stress.

Although granule cells continue to be added to the dentate gyrus of adult rats and tree shrews, this phenomenon has not been demonstrated in the dentate gyrus of adult primates. To determine whether neurons are produced in the dentate gyrus of adult primates, adult marmoset monkeys (Callithrix jacchus) were injected with BrdU and perfused 2 hr or 3 weeks later. BrdU is a thymidine analog that is incorporated into proliferating cells during S phase. A substantial number of cells in the dentate gyrus of adult monkeys incorporated BrdU and approximately 80% of these cells had morphological characteristics of granule neurons and expressed a neuronal marker by the 3-week time point. Previous studies suggest that the proliferation of granule cell precursors in the adult dentate gyrus can be inhibited by stress in rats and tree shrews. To test whether an aversive experience has a similar effect on cell proliferation in the primate brain, adult marmoset monkeys were exposed to a resident-intruder model of stress. After 1 hr in this condition, the intruder monkeys were injected with BrdU and perfused 2 hr later. The number of proliferating cells in the dentate gyrus of the intruder monkeys was compared with that of unstressed control monkeys. We found that a single exposure to this stressful experience resulted in a significant reduction in the number of these proliferating cells. Our results suggest that neurons are produced in the dentate gyrus of adult monkeys and that the rate of precursor cell proliferation can be affected by a stressful experience.

Animals↗

An Epstein-Barr-related herpesvirus from marmoset lymphomas.

Epstein-Barr virus (EBV) is implicated in the development of human B cell lymphomas and carcinomas. Although related oncogenic herpesviruses were believed to be endemic only in Old World primate species, we now find these viruses to be endemic in New World primates. We have isolated a transforming, EBV-related virus from spontaneous B cell lymphomas of common marmosets (Callithrix jacchus). Sequencing of two-thirds of the genome reveals considerable divergence from the genomes of EBV and Old World primate EBV-related viruses, including differences in genes important for virus-induced cell growth transformation and pathogenesis. DNA related to the C. jacchus herpesvirus is frequently detected in squirrel monkey peripheral blood lymphocytes, indicating that persistent infection with EBV-related viruses is prevalent in both New World primate families. Understanding how these more divergent EBV-related viruses achieve similar biologic outcomes in their natural host is likely to provide important insights into EBV infection, B cell growth transformation, and oncogenesis.

Amino Acid Sequence↗

Fetal globin expression in New World monkeys.

Reverse phase chromatography of the globin chains of adult, newborn, and fetal erythrocytes from three species of New World monkeys (Cebus apella, Aotus azarae, and Callithrix jacchus) representing three of the seven platyrrhine clades showed that gamma-globin expression was fetal in these animals. The globins were identified by a combination of chemical sequencing and mass spectrometric analysis. Since gamma-globin expression is fetal in the other major simian branch, the catarrhines, but embryonic in prosimian primates and nonprimate placental mammals, the evolution of fetal recruitment can now be assigned to the period between the simian-prosimian divergence (55 million years ago) and the platyrrhine-catarrhine divergence (35 million years ago). The gamma-globin gene underwent tandem duplication during the same evolutionary epoch, in accord with a model that suggests that the downstream duplicated gamma-gene (gamma2) was free to acquire the mutations necessary for fetal recruitment. Mass spectrometric analysis of tryptic digests of the gamma-globins verified the amino acid sequences deduced from genomic sequencing. Detailed analysis of high performance liquid chromatography and matrix-assisted laser desorption/ionization mass spectrometry data showed that gamma2-globin in Cebus was expressed to a far greater extent than gamma1-globin, supporting inferences drawn from a study of the promoter sequences. A "pre-gamma"-globin was observed in C. apella and shown to be primarily the glutathionyl adduct. The other species, A. azarae and C. jacchus, also express only one gamma-globin polypeptide. This work provides biochemical evidence of an evolutionary trend in the platyrrhines to alter the duplicated gamma-globin gene locus so that only one gamma-globin polypeptide is expressed.

Abortion, Veterinary↗

Evolution of the primate cathelicidin. Correlation between structural variations and antimicrobial activity.

Cathelicidin genes homologous to the human CAMP gene, coding for the host defense peptide LL-37, have been sequenced and analyzed in 20 primate species, including Great Apes, hylobatidae, cercopithecidae, callithricidae, and cebidae. The region corresponding to the putative mature antimicrobial peptide is subject to a strong selective pressure for variation, with evidence for positive selection throughout the phylogenetic tree relating the peptides, which favors alterations in the charge while little affecting overall hydrophobicity or amphipathicity. Selected peptides were chemically synthesized and characterized, and two distinct types of behavior were observed. Macaque and leaf-eating monkey RL-37 peptides, like other helical antimicrobial peptides found in insect, frog, and mammalian species, were unstructured in bulk solution and had a potent, salt and medium independent antimicrobial activity in vitro, which may be the principal function also in vivo. Human LL-37 and the orangutan, hylobates, and callithrix homologues instead showed a salt-dependent structuring and likely aggregation in bulk solution that affected antimicrobial activity and its medium dependence. The two types of peptides differ also in their interaction with host cells. The evolution of these peptides has thus resulted in distinct mechanisms of action that affect the direct antimicrobial activity and may also modulate accessory antimicrobial functions due to interactions with host cells.

Amino Acid Sequence↗

Elevated urinary excretion of beta-aminoisobutyric acid and exposure to inorganic lead.

beta-Aminoisobutyric acid (beta-AIB), a normal degradation product of thymine, a constituent of DNA and, to a lesser extent, of transfer RNA, is excreted in low levels in human urine. We found that a group of iron workers occupationally exposed to inorganic lead excreted high levels of urinary beta-AIB. Elevated urinary excretion of beta-AIB was also observed in marmosets, Callithrix jacchus, that received lead acetate in drinking water. Our results suggest that increased urinary excretion of beta-AIB could stem from damage to DNA on exposure to lead.

Adult↗

Spontaneous lesions of the cardiovascular system in purpose-bred laboratory nonhuman primates.

This retrospective study was performed to determine the range, occurrence and incidence of spontaneously arising histopathological findings of the cardiovascular system in purpose-bred laboratory nonhuman primates. Data were collected from 84 controlled toxicological studies with equal numbers of male and female animals and full tissue lists. Attempts were also made to standardize pathological terms used by various original pathologists. Tissue sections from 2464 animals, which included 2050 cynomolgus monkeys (Macaca fascicularis), 284 common marmosets (Callithrix jacchus) and 130 rhesus monkeys (Macaca mulatta) were examined. The most common cardiac finding was focal myocardial inflammation, subcategorized as either "inflammatory cell infiltration" (339) or "focal myocarditis" (131). Other cardiac findings included mineralization (29), endocarditis (16), pericarditis (10), squamous cysts (6) and ectopic thyroid tissue (5). Perivasculitis/vasculitis in the kidney, lung, meninges, sciatic nerve, and other tissues (206) was the most common vascular lesion. Focal myocarditis was more common in male (60%) than female (40%) animals. Cardiac mineralization and extramedullary hematopoiesis were more common in marmosets than other species while ectopic thyroid tissue was present in marmosets and cynomolgus monkeys. To our knowledge, this is the first study to demonstrate the range and incidence of spontaneous cardiovascular lesions in laboratory nonhuman primates.

Animals↗

Behavioural analysis of unilateral monoamine depletion in the marmoset.

Unilateral stereotaxic injections of 6-hydroxydopamine (6-OHDA) into the nigrostriatal bundle of marmosets (Callithrix jacchus) produced substantial losses of tyrosine hydroxylase immunoreactive neurons from the substantia nigra, and mean dopamine (DA) depletions of 98-99% in the caudate nucleus, putamen and nucleus accumbens, and of 91-97% in frontal cortex, on the side of the lesion. Noradrenaline (NA) and 5-hydroxytryptamine (5-HT) levels were also affected. Behavioural tests conducted pre-operatively and at regular intervals during the 6 mths following surgery revealed persistent deficits in the lesioned marmosets as a group compared with sham-lesioned controls, although individual marmosets sometimes recovered or showed no initial deficit on some tests. The main behavioural effects of the lesion were as follows: (i) an increase in the time spent with the head positioned ipsilaterally with respect to the rest of the body; (ii) ipsilateral spontaneous and amphetamine-induced rotation, although occasional intermittent periods of contralateral rotation and head biases were also recorded; (iii) contralateral apomorphine-induced rotation; (iv) reduced spontaneous activity; (v) ipsilateral hand preference on a conveyor belt task, although hand skill (measured as percentage errors when the speed of the belt was increased) was not affected; (vi) neglect of contralateral stimuli, both at the conveyor belt where lesioned monkeys often failed to respond on trials on which apple pieces arrived from the contralateral side, and on a test of sensorimotor neglect in which adhesive labels were placed around both feet. Comparisons of biochemical measures of the lesion with behavioural scores in individual monkeys suggest that DA depletions in excess of 95% are essential for long-term behavioural deficits.

Animals↗

Primary CA1 and conditionally immortal MHP36 cell grafts restore conditional discrimination learning and recall in marmosets after excitotoxic lesions of the hippocampal CA1 field.

Common marmosets (Callithrix jacchus, n = 18) were trained to discriminate between rewarded and non-rewarded objects (simple discriminations, SDs) and to make conditional discriminations (CDs) when presented sequentially with two different pairs of identical objects signifying reward either in the right or left food well of the Wisconsin General Test Apparatus. After bilateral N-methyl-D-aspartate (0.12 M) lesions through the cornu ammonis-1 (CA1) field (7 microl in five sites), marmosets showed profound impairment in recall of CDs but not SDs, and were assigned to lesion only, lesion plus CA1 grafts and lesion plus Maudsley hippocampal cell line, clone 36 (MHP36) grafts groups matched for lesion-induced impairment. Cell suspension grafts (4 microl, 15-25 000 cells/microl) of cells dissected from the CA1 region of foetal brain at embryonic day 94-96, or of conditionally immortalized MHP36 cells, derived from the H-2Kb-tsA58 transgenic mouse neuroepithelium and labelled with [3H]thymidine, were infused at the lesion sites. The lesion plus MHP36 grafts group was injected five times per week with cyclosporin A (10 mg/kg) throughout testing. Lesion, grafted and intact control marmosets (n = 4-5/group) were tested on recall of SDs and CDs learned before lesioning and on acquisition of four new CDs over a 6-month period. Lesioned animals were highly impaired in recall and acquisition of CD tasks, but recall of SDs was not significantly disrupted. Both grafted groups of marmosets showed improvement to control level in recall of CDs. They were significantly slower in learning the first new CD task, but mastered the remaining tasks as efficiently as controls and were substantially superior to the lesion-only group. Visualized by Nissl staining, foetal grafts formed clumps of pyramidal-like cells within the denervated CA1 field, or jutted into the lateral ventricles. MHP36 cells, identified by beta-galactosidase staining and autoradiography, showed neuronal and astrocytic morphology, and were distributed evenly throughout the CA1 region. The results indicate that MHP36 cell grafts are as functionally effective as foetal grafts and appear to integrate into the host brain in a structurally appropriate manner, showing the capacity to differentiate into both mature neurons and glia, and to develop morphologies appropriate to the site of migration. These findings, which parallel the facilitative effects of foetal and MHP36 grafts in rats with ischaemic CA1 damage, offer encouragement for the development of conditionally immortal neuroepithelial stem cell lines for grafting in conditions of severe amnesia and hippocampal damage following recovery from cardiac arrest or other global ischaemic episodes.

Animals↗

Vascularization in the primate visual cortex during development.

We studied the relationship between vascularization and neuronal activity in the visual cortex during postnatal development in the primate. Analyses were focused on layer IVC that displays a sequential pattern of maturation for the magno- and parvocellular systems in separate sublayers, respectively IVC alpha and IVC beta. Cytochrome oxidase and endogenous alkaline phosphatase histochemistry was used to analyse, on the same sections, the laminar patterns of cortical activity and vessel density in the primary visual cortex of the marmoset (Callithrix jacchus). Experiments were carried out in five young and two adult animals. We showed that the temporal pattern of angiogenesis differs in layer IVC alpha and IVC beta. During the first postnatal month, vessel density is higher in IVC alpha than in IVC beta and runs parallel to cytochrome oxidase intensity. In 2-month-old animals, both vessel densities and cytochrome oxidase activity are similar in IVC alpha and IVC beta. In adults, the vessel densities in IVC alpha and IVC beta are the reverse of those observed during the first postnatal month. Vessel diameter does not account for this evolution in vascular patterns. In the discussion, we suggest that such a developmental time-course of angiogenesis might be linked to the synaptogenesis requirements that proceed differently for the magno- and parvocellular systems in the primate striate cortex.

Alkaline Phosphatase↗

Identification of V1R-like putative pheromone receptor sequences in non-human primates. Characterization of V1R pseudogenes in marmoset, a primate species that possesses an intact vomeronasal organ.

The vomeronasal organ (VNO) is responsible in terrestrial vertebrates for the sensory perception of some pheromones, chemicals that elicit characteristic behaviors among individuals of the same species. Two multigene families (V1R, V2R) that encode proteins with seven putative transmembrane domains that are expressed selectively in different neuron subsets of the VNO have been described in rodents. Pheromone-induced behaviors and a functional VNO have been described in a number of mammals, but this sensory organ seems absent in adult catarrhines and apes, including humans. Until now, only pseudogenes have been isolated in humans, except one putative V1R (hV1RL1) sequence expressed in the main olfactory epithelium. We sought to isolate V1R-like genes in a New World monkey species, the marmoset Callithrix jacchus, that possesses an intact VNO and for which pheromone-induced behavior has been well documented. Using library screening approaches, we have identified five different sequences that exhibit characteristic features of V1R sequences, but that are non-functional pseudogenes. In an attempt to sort out functional V1R genes, we next cloned by polymerase chain reaction (PCR) the primate orthologues of hV1RL1. This approach was successful for gorilla, chimpanzee and orangutan, but not for the other species, including marmoset, probably because these species are too divergent from humans. Chimpanzee and orangutan V1RL1 genes are pseudogenes, whereas the gorilla counterpart is potentially functional. These observations raise the possibility that the V1R family has evolved in such a manner in mammals that every species that relies on a VNO-mediated sensory function possesses its own set of functional vomeronasal genes.

Amino Acid Sequence↗