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A complete genome for the common marmoset.

The common marmoset is a New World monkey widely used to study primate evolution and human disease. We present a telomere-to-telomere (T2T) reference assembly for the species, plus three near-T2T haplotypes. These resolve previously inaccessible regions, including the centromeres, sex chromosomes, subterminal satellites, acrocentric chromosomes, and the major histocompatibility complex (MHC). We find marmoset centromeres carry dimeric alpha satellites with chromosomal specificity, flanked by inactive layers interpreted as ancestral centromere remnants. We assemble gene-poor, satellite-rich short arms of the acrocentrics and find that most can harbor rDNA and all share pseudo-homolog regions (PHRs). PHR-sharing chromosomes also share closely related centromeric satellites, consistent with a model of ongoing rDNA-facilitated recombinational exchange between heterologous chromosomes. We further identify over 500 marmoset-lineage-specific transcribed genes with previously unknown transcript models or expansions. These resources, along with a preliminary pangenome, improve the utility of the marmoset as a model organism and address gaps in primate genome evolution.

Animals

Susceptibility of common marmosets (Callithrix jacchus) to oncogenic and attenuated strains of Herpesvirus saimiri.

Adult common marmosets, inoculated with either of 2 oncogenic Herpesvirus saimiri (HVS) strains, developed fatal lymphoproliferative disease within 23-25 days post inoculation (PI). The disease was identical to HVS-induced lymphoma in cotton-topped and white-lipped marmosets. Common marmosets inoculated with an attenuated HVS strain developed persistent infection; virus has been recovered from cocultivated lymphocytes of these animals for more than 384 days PI.

Animals

The common marmoset (Callithrix jacchus jacchus) as a model for ethological research.

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.

Aggression

Use of the common marmoset, Callithrix jacchus, in reproductive research.

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.

Aging

Density distribution, characterization, and comparative aspects of the major serum lipoproteins in the common marmoset (Callithrix jacchus), a New World primate with potential use in lipoprotein research.

Qualitative, quantitative, and comparative aspects of the serum lipoprotein profile in the Common marmoset (Callithrix jacchus), a New World primate, are described. Density gradient ultracentrifugation was used to evaluate lipoprotein distribution and to establish criteria for isolation of discrete molecular fractions. The major lipoprotein classes banded isopycnically on the gradient with the following hydrated densities: VLDL, d less than 1.017 g/mL; LDL, d = 1.027--1.055 g/mL; HDL fraction I, d = 1.070--1.127 g/mL; and HDL fraction II, d = 1.127--1.156 g/mL. Electrophoretic, immunological, and electron microscopic analyses attested to the purity of these fractions: the characteristics of each were assessed by chemical analysis, electron microscopy, immunological techniques, and polyacrylamide gel electrophoresis of their protein moieties. Marmoset VLDL and LDL were closely akin to those of man in size and chemical composition, although the former were richer in triglyceride; electrophoretic and immunological data showed the major protein component of VLDL and LDL to be a counterpart to human apo-B. The two HDL subfractions, i.e., HDL-I and HDL-II, corresponded in size and chemical composition to human HDL2 and HDL3, respectively, although slight differences in neutral lipid content were detected. By immunological and electrophoretic criteria, the major apolipoprotein of marmoset HDL was analogous to human apo-AI. In contrast, marked dissimilarities were evident in the complements of low molecular weight, tetramethylurea-soluble polypeptides of marmoset and human lipoproteins. Quantitatively, the human and marmoset lipoprotein profiles were not dissimilar, although HDL was the major class (approximately 50%); in fasting animals, serum concentrations of VLDL, LDL, and HDL were 50--90, 170--280, and 338--408 mg/dL, respectively. C. jacchus was distinct from man in displaying a greater proportion of its total HDL in the less dense (HDL-II) subfraction (marmoset HDL-I/HDL-II = approximately 4:1; human HDL2/HDL3 = approximately 1:3). These data indicate that, as an experimental animal for lipoprotein research, the Common marmoset combines the advantages of ready availability and maintenance with a serum lipoprotein profile which resembles, in many qualitative and quantitative aspects, that found in man.

Animals

Sex determination in the common marmoset (Callithrix jacchus).

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.

Animals

Establishment of a Common Marmoset Lineage Carrying a Frameshift Mutation in SETD1A, a Schizophrenia Risk Gene.

Appropriate histone modifications are essential for maintaining functional chromatin structure and gene expression, and dysfunction of their regulators has been linked to a variety of diseases. Among these modifications, trimethylation of lysine 4 on histone H3 (H3K4me3) is a well-characterized epigenetic mark enriched at transcription start sites of actively transcribed genes. H3K4me3 regulates gene transcription by recruiting transcription factors, facilitating chromatin accessibility, and preventing DNA methylation. In mammals, methylation of H3K4 is catalyzed by a family of histone methyltransferases including SET domain containing 1A (SETD1A), which is primarily responsible for genome-wide deposition of H3K4me2/3. Loss-of-function variants in SETD1A, highlighting its critical role in brain development and cognitive function, are strongly associated with schizophrenia (SCZ) and other neurodevelopmental disorders, but the underlying mechanisms remain largely unclear. To better understand the epigenetic and neurobiological consequences of SETD1A dysfunction, non-human primate models can serve as a useful tool because of their close evolutionary relationship to humans and highly developed cognitive abilities. In this study, we established a genetically engineered common marmoset (Callithrix jacchus) lineage carrying a frameshift mutation in SETD1A, which is, to the best of our knowledge, the first non-human primate lineage carrying a mutation in an epigenetic regulatory gene associated with SCZ, and confirmed germline transmission of the mutant allele. In a comparison between fibroblasts derived from one SETD1A mutant and one wild-type marmoset, the mutant showed a lower SETD1A protein level, modest differences in H3K4me3 deposition, and broader differences in gene expression profiles. Although these molecular observations require validation using additional biological replicates, the establishment of this SETD1A mutant marmoset lineage provides a valuable platform for bridging molecular mechanisms with primate neurobiology and for investigating the role of epigenetic regulation in the pathophysiology of neuropsychiatric and neurodevelopmental disorders.

Animals

Bacterial and mycoplasma flora of a laboratory colony of the common marmoset (Callithrix jacchus).

A survey was carried out to characterise the bacterial and mycoplasma flora of a closed colony of marmosets, Callithrix jacchus. Bordetella bronchiseptica and Staphylococcus aureus were the only potential bacterial pathogens isolated from the colony; Candida albicans was also identified. S aureus and C albicans were the only organisms which were associated with macroscopic lesions or overt disease. Post mortem examination of the animals proved only reliable method of establishing the presence of some bacterial species in the colony, eg, B bronchiseptica and of obtaining a reliable estimate of the incidence of the various organisms within the colony. The marmosets were all infected with ureaplasmas in the upper respiratory tract. Mycoplasma salivarium was isolated from this site in several animals. There was no evidence to indicate that cross-infection had occurred between the animal technicians and the marmosets, except in one possible case of candidiasis.

Animals

Composition of the milk of the common marmoset (Callithrix jacchus) and milk substitutes used in hand-rearing programmes, with special reference to fatty acids.

Analyses of marmoset (Callithrix jacchus) milk were carried out to determine values for crude protein, lactose, total lipids, major minerals, and osmotic pressure. Mean values were (g/100 ml): protein, 3.6; lactose, 7.5; total lipids, 7.7; minerals (mg/100 ml): sodium, 21.4; potassium, 54.3; calcium, 92.2; phosphorus, 22.8; magnesium, 5.0; chloride, 52.2; osmotic pressure, 354 mosm/kg water. Similar analyses were conducted on 2 milk substitutes used in hand-rearing programmes. Fatty acid analyses were carried out on natural milk, the milk substitutes, and the marmoset diet. For hand-rearing C. jacchus it is recommended that a human milk substitute is modified by increasing the levels of protein, carbohydrate, and total lipids, and that a small amount of fish oil is added.

Animal Feed

Pregnancy diagnosis in the common marmoset (Callithrix jacchus jacchus).

Abdominal palpation of the uterus was carried out on 25 pregnant and 29 non-pregnant marmosets (Callithrix jacchus jacchus). 195 complete 24-hour urine specimens, collected between the first week of gestation and term (21 weeks), were tested with the Sub-Human Primate Tube (SHPT) test. No significant differences between the two methods in their ability to diagnose pregnancy were obtained between the first and 13th week of gestation. The SHPT test was seldom positive after the 13th week of pregnancy, whereas, with one exception, palpation always indicated pregnancy.

Animals

Epstein-Barr virus: experimental infection of Callithrix jacchus marmosets.

Eight common marmoset monkeys (Callithrix jacchus) were inoculated with about 10(4) transforming units of B95-8 virus; seven of the marmosets died 50-111 days post inoculation and all seven showed microscopic and/or macroscopic lesions compatible with a diagnosis of lymphoproliferative disease. Low levels of anti-VCA antibodies were detected in plasma from six marmosets. Attempts failed to establish continuous EBV-carrying lymphoblastoid cell cultures by cultivation in vitro of circulating lymphocytes or minced lymphoid tissues obtained at necropsy.

Animals

Plasmodium knowlesi in the marmoset (Callithrix jacchus).

Common marmosets were shown to be susceptible to Plasmodium knowlesi malaria. The morphology of the parasite was indistinguishable from the observed in the natural host (Macaca fascicularis) and the common laboratory model (Macaca mulatta). A differential susceptibility to P. knowlesi was observed in the 8 marmosets studied. Multiplication rates of parasites were variable over 24 h periods. Five animals died of a fulminating infection within 12--17 days after challenge. Three animals recovered spontaneously from infection and were subsequently resistant to challenge with homologous and heterologous variants and strains of P. knowlesi. This resistance was maintained for intervals up to 100 days between challenge infections.

Animals

Experimental infection of Callithrix Jacchus marmosets with Herpesvirus ateles, Herpesvirus saimiri, and Epstein Barr virus.

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.

Animals

Aggression and flight behaviour of the marmoset monkey Callithrix jacchus: an ethogram for brain stimulation studies.

The aggressive and flight behaviour of the common marmoset monkey (Callithrix jacchus) is described and split into behavioural units, allowing analysis of agonistic behaviour evoked by electrical stimulation of the hypothalamus. The social context of the described units is also considered. C. jacchus shows clearly recognizable behavioural patterns. Free-born animals are very timid and show typical flight reactions. Within aggressive behaviour, two types of aggression can be distinguished: very violent attacks causing severe injuries, often accompanied by particular threat displays and observed during dominance and territorial encounters, and, on the other hand, relatively harmless short attacks, together with a noisy vocalization, for defensive purposes or keeping group members at a distance.

Aggression

Yersinia enterocolitica infections in non-human primates.

Yersinia enterocolitica was isolated from ten non-human primates in the Netherlands. The following species were represented: Potto, Senegalgalago, wooly monkey, black spider monkey, common marmoset, cottonhead tamarin, pigtailed macaque and lesser whitenosed guenon.

Animals

Overview of viral oncology studies in Saguinus and Callithrix species.

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.

Age Factors

Indoor-outdoor housing systems for a self-sustaining marmoset breeding colony.

Indoor-outdoor housing of three types was designed, constructed, used and evaluated for housing a breeding colony of common (Callithrix jacchus) and cottontop (Saguinus oedipus) marmosets. All types were relatively inexpensive to construct, required minimal care, simulated a natural environment and allowed for some isolation between units and between individual runs within units.

Animals