Project description:We identified a novel repeat family, termed Platy-1, in the Callithrix jacchus (common marmoset) genome that arose around the time of the divergence of platyrrhines and catarrhines and established itself as a repeat family in New World monkeys (NWMs). A full-length Platy-1 element is ∼100 bp in length, making it the shortest known short interspersed element (SINE) in primates, and harbors features characteristic of non-LTR retrotransposons. We identified 2268 full-length Platy-1 elements across 62 subfamilies in the common marmoset genome. Our subfamily reconstruction and phylogenetic analyses support Platy-1 propagation throughout the evolution of NWMs in the lineage leading to C. jacchus Platy-1 appears to have reached its amplification peak in the common ancestor of current day marmosets and has since moderately declined. However, identification of more than 200 Platy-1 elements identical to their respective consensus sequence, and the presence of polymorphic elements within common marmoset populations, suggests ongoing retrotransposition activity. Platy-1, a SINE, appears to have originated from an Alu element, and hence is likely derived from 7SL RNA. Our analyses illustrate the birth of a new repeat family and its propagation dynamics in the lineage leading to the common marmoset over the last 40 million years.
Project description:Currently, the amount of sequenced and classified MHC class I genes of the common marmoset is limited, in spite of the wide use of this species as an animal model for biomedical research. In this study, 480 clones of MHC class I G locus (Caja-G) cDNA sequences were obtained from 21 common marmosets. Up to 10 different alleles were detected in each common marmoset, leading to the assumption that the Caja-G loci duplicated in the marmoset genome. In the investigated population, four alleles occurred more often, giving evidence for higher immunological advantage of these alleles. In contrast to the human non-classical MHC class I genes, Caja-G shows high rates of polymorphism at the relevant peptide-binding sites, despite its phylogenetic relationship to the non-classical HLA-G. Our results provide information for better understanding of the immunological properties of the common marmoset and confirm the theory of a gene conversion of the Caja-G due to its detected plasticity and the absence of any known HLA-A equivalent.
Project description:The common marmoset (Callithrix jacchus) is a non-human primate that could prove useful as human pharmacokinetic and biomedical research models. The cytochromes P450 (P450s) are a superfamily of enzymes that have critical roles in drug metabolism and disposition via monooxygenation of a broad range of xenobiotics; however, information on some marmoset P450s is currently limited. Therefore, identification and quantitative analysis of tissue-specific mRNA transcripts, including those of P450s and flavin-containing monooxygenases (FMO, another monooxygenase family), need to be carried out in detail before the marmoset can be used as an animal model in drug development. De novo assembly and expression analysis of marmoset transcripts were conducted with pooled liver, intestine, kidney, and brain samples from three male and three female marmosets. After unique sequences were automatically aligned by assembling software, the mean contig length was 718 bp (with a standard deviation of 457 bp) among a total of 47,883 transcripts. Approximately 30% of the total transcripts were matched to known marmoset sequences. Gene expression in 18 marmoset P450- and 4 FMO-like genes displayed some tissue-specific patterns. Of these, the three most highly expressed in marmoset liver were P450 2D-, 2E-, and 3A-like genes. In extrahepatic tissues, including brain, gene expressions of these monooxygenases were lower than those in liver, although P450 3A4 (previously P450 3A21) in intestine and P450 4A11- and FMO1-like genes in kidney were relatively highly expressed. By means of massive parallel long-read sequencing and short-read technology applied to marmoset liver, intestine, kidney, and brain, the combined next-generation sequencing analyses reported here were able to identify novel marmoset drug-metabolizing P450 transcripts that have until now been little reported. These results provide a foundation for mechanistic studies and pave the way for the use of marmosets as model animals for drug development in the future.
Project description:An improved de novo genome assembly of the common marmoset genome yields improved contiguity and increased mapping rates of sequence data
Project description:Background:Recently, the use of common marmoset (Callithrix jacchus) has increased in biomedical research as an animal model. This study aimed to test fecal samples to monitor bacterial and parasite infections in common marmoset at the Laboratory Animal Center of Osong Medical Innovation Foundation in Korea. Methods:To monitor bacteria and parasites in common marmoset, we tested 43 fecal samples of 43 common marmosets by culture and parasitological test in 2014. Infection by Chilomastix mesnili was determined by PCR method. Results:We identified nonpathogenic bacteria such as Proteus mirabilis and Escherichia coli in feces of normal common marmosets. Interestingly, C. mesnili was isolated from a healthy common marmoset by fecal centrifugation concentration and PCR. The monkey infected with C. mesnili was treated with metronidazole. After the treatment, C. mesnili were not found in feces using fecal centrifugation concentration and PCR. Conclusion:This is the first case report of C. mesnili infection in common marmoset. Treatment with metronidazole is found to be highly effective in eradicating C. mesnili infection in common marmoset.
Project description:The marmoset (Callithrix jacchus) is a valuable non-human primate model for studying behavioral and neural mechanisms related to vocal communication. It is also well suited for investigating neural mechanisms related to cochlear implants. The purpose of this study was to characterize marmoset temporal bone anatomy and investigate the feasibility of implanting a multi-channel intracochlear electrode into the marmoset scala tympani. Micro computed tomography (microCT) was used to create high-resolution images of marmoset temporal bones. Cochlear fluid spaces, middle ear ossicles, semicircular canals and the surrounding temporal bone were reconstructed in three-dimensional space. Our results show that the marmoset cochlea is ?16.5 mm in length and has ?2.8 turns. The cross-sectional area of the scala tympani is greatest (?0.8 mm(2)) at ?1.75 mm from the base of the scala, reduces to ?0.4 mm(2) at 5 mm from the base, and decreases at a constant rate for the remaining length. Interestingly, this length-area profile, when scaled 2.5 times, is similar to the scala tympani of the human cochlea. Given these dimensions, a compatible multi-channel implant electrode was identified. In a cadaveric specimen, this electrode was inserted ¾ turn into the scala tympani through a cochleostomy at ?1 mm apical to the round window. The depth of the most apical electrode band was ?8 mm. Our study provides detailed structural anatomy data for the middle and inner ear of the marmoset, and suggests the potential of the marmoset as a new non-human primate model for cochlear implant research.
Project description:To safeguard patients, regulatory authorities require that new drugs that are to be given by the intravitreal (IVT) route are assessed for their safety in a laboratory species using the same route of administration. Due to the high similarity of ocular morphology and physiology between humans and nonhuman primates (NHPs) and due to the species specificity of many biotherapeutics, the monkey is often the only appropriate model. To this end, intravitreal administration and assessment of ocular toxicity are well established in cynomolgus monkeys (Macaca fascicularis). In contrast, the common marmoset monkey (Callithrix jacchus) is not a standard model for ocular toxicity studies due to its general sensitivity to laboratory investigations and small eye size. It was the purpose of the present work to study whether the marmoset is a useful alternative to the cynomolgus monkey for use in intravitreal toxicological studies. Six marmoset monkeys received repeated (every 2 weeks for a total of four doses) intravitreal injections of 10 or 20? µ L of a placebo. The animals were assessed for measurements of intraocular pressure (IOP), standard ophthalmological investigations and electroretinography (ERG). At the end of the dosing period, the animals were sacrificed and the eyes were evaluated histologically. ERG revealed similar results when comparing predose to end-of-study data, and there was no difference between the two dose volumes. A transient increase in the IOP was seen immediately after dosing, which was more pronounced after dosing of 20? µ L compared to 10? µ L. Ophthalmologic and microscopic observations did not show any significant changes. Therefore, it can be concluded that 10? µ L as well as 20? µ L intravitreal injections of a placebo are well tolerated in the marmoset. These results demonstrate that the common marmoset is an alternative to the cynomolgus monkey for intravitreal toxicity testing.