Overview of the marmoset as a model in nonclinical development of pharmaceutical products

Orsi, Antonia; Rees, Daryl; Andreini, Isabella; Venturella, Silvana; Cinelli, Serena; Oberto, Germano

doi:10.1016/j.yrtph.2010.12.003

Cited by 65 publications

(62 citation statements)

References 82 publications

(92 reference statements)

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“…In the present study, we describe the small RNA profile from the adult testes of the common marmoset, a small New World primate, which has been attracting much attention in the research field of biomedical sciences as a model primate species (Sasaki et al 2009;Orsi et al 2011;Okano et al 2012). Our small RNA profiling confirmed the importance of using the common marmoset to analyze primates.…”

Section: Discussionsupporting

confidence: 63%

“…Marmosets are small New World monkeys that have been extensively used in biomedical research and provide an attractive alternative to traditional nonhuman primate species. This is mainly because (1) they reach sexual maturity at 18 months of age, (2) they often bear twins after a relatively short gestation period, and (3) transgenic animals can now be produced (Sasaki et al 2009;Orsi et al 2011;Okano et al 2012). To gain insights into the function of small RNAs in the marmoset testis, we used small RNA sequencing (small RNA-seq) to generate extensive small RNA data, in conjunction with RNA-seq data.…”

Section: Introductionmentioning

confidence: 99%

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Small RNA profiling and characterization of piRNA clusters in the adult testes of the common marmoset, a model primate

Hirano

Iwasaki

Lin

et al. 2014

RNA

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Small RNAs mediate gene silencing by binding Argonaute/Piwi proteins to regulate target RNAs. Here, we describe small RNA profiling of the adult testes of Callithrix jacchus, the common marmoset. The most abundant class of small RNAs in the adult testis was piRNAs, although 353 novel miRNAs but few endo-siRNAs were also identified. MARWI, a marmoset homolog of mouse MIWI and a very abundant PIWI in adult testes, associates with piRNAs that show characteristics of mouse pachytene piRNAs. As in other mammals, most marmoset piRNAs are derived from conserved clustered regions in the genome, which are annotated as intergenic regions. However, unlike in mice, marmoset piRNA clusters are also found on the X chromosome, suggesting escape from meiotic sex chromosome inactivation by the X-linked clusters. Some of the piRNA clusters identified contain antisenseorientated pseudogenes, suggesting the possibility that pseudogene-derived piRNAs may regulate parental functional proteincoding genes. More piRNAs map to transposable element (TE) subfamilies when they have copies in piRNA clusters. In addition, the strand bias observed for piRNAs mapped to each TE subfamily correlates with the polarity of copies inserted in clusters. These findings suggest that pachytene piRNA clusters determine the abundance and strand-bias of TE-derived piRNAs, may regulate protein-coding genes via pseudogene-derived piRNAs, and may even play roles in meiosis in the adult marmoset testis.

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Section: Discussionsupporting

confidence: 63%

Section: Introductionmentioning

confidence: 99%

Small RNA profiling and characterization of piRNA clusters in the adult testes of the common marmoset, a model primate

Hirano

Iwasaki

Lin

et al. 2014

RNA

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show abstract

“…The common marmoset (Callithrix jacchus) has been utilized as a non-human primate model for nonclinical pharmaceutical development (Orsi et al, 2011). The common marmoset's importance as a model in biomedical research will be enhanced with the recent publication of its genome (Worley et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

Isolation and characterization of a novel Helicobacter species, Helicobacter jaachi sp. nov., from common marmosets (Callithrix jaachus)

Shen

Feng

Sheh

et al. 2015

Journal of Medical Microbiology

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Isolation and characterization of a novelHelicobacter species, Helicobacter jaachi sp. nov., from common marmosets (Callithrix jaachus) Purpose-bred common marmosets from domestic sources housed in a US research facility, and used in multiple drug discovery programmes, were noted to have a high incidence of spontaneous inflammatory bowel disease and sporadic cholecystitis and cholangiohepatitis. Inflammatory infiltrates increased in incidence and severity with age. Because Helicobacter spp. have been linked to gastrointestinal diseases, samples from the gastrointestinal tracts of 39 marmosets were screened for Helicobacter spp. by culture and PCR. Helicobacter spp. were frequently detected in marmosets; 28.2 % of the marmosets were positive for a proposed novel species, Helicobacter jaachi sp. nov., by culture, and 48.7 % were positive by Helicobacter genus-specific PCR. Seventeen strains of Helicobacter sp. from 11 marmosets were cultured from various gastrointestinal sites. Older animals (age 6-11 years) had a higher helicobacter prevalence rate (57.1 %) compared with younger animals (age 3-5 years), which had a 27.2 % prevalence rate. Cells of H. jaachi sp. nov. were catalase, urease and oxidase positive and had fusiform morphology, with periplasmic fibres and multiple bipolar, sheathed flagella. All isolates had similar 16S and 23S rRNA sequences, which clustered as representatives of a novel Helicobacter species closely related to 'Helicobacter sanguini' (97 %), a species isolated from cotton-top tamarins and 'Helicobacter callitrichis' (96 %) isolated previously from the faeces of common marmosets. The whole genome sequence of one of the liver isolates, H. jaachi sp. nov. MIT 09-6949 T , had a 1.9 Mb genome length with a 41 mol% DNA G+C content. The type strain of Helicobacter jaachi sp. nov., MIT 09-6949 T , has been deposited in the BCCM/LMG Bacteria Collection as LMG 28613 T . These findings add to the increasing number of animal species with gastrointestinal disease in which novel enterohepatic Helicobacter spp. have been isolated. INTRODUCTIONThe common marmoset (Callithrix jacchus) has been utilized as a non-human primate model for nonclinical pharmaceutical development (Orsi et al., 2011). The common marmoset's importance as a model in biomedical research will be enhanced with the recent publication of its genome (Worley et al., 2014). An illustration of the marmoset's usefulness is its use in neuroscience research and genome editing technology (Kishi et al., 2014). A small common marmoset colony was established at GlaxoSmithKline to serve as a preclinical model for drug discovery and development. Common marmosets develop diet-induced obesity phenotypes when placed on high fat diets and were employed in studies to help develop anti-obesity compounds (Tardif et al., 2009). Over the course of several years, complete necropsies were performed on 46 marmosets originating from this colony. The spectrum of spontaneous pathology documented was similar to that reported in the literature for common marmoset...

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“…Common marmosets (Callithrix jacchus), belonging to New World monkeys, are attractive as small non-human primate models in drug metabolism studies due to genetic closeness, small body size, early sexual maturity, and high reproductive efficacy (Orsi et al, 2011;Sasaki, 2015).…”

Section: Introductionmentioning

confidence: 99%

Molecular Cloning, Tissue Distribution, and Functional Characterization of Marmoset Cytochrome P450 1A1, 1A2, and 1B1

Uehara

Uno

Inoue

et al. 2015

Drug Metabolism and Disposition

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The common marmoset (Callithrix jacchus), a New World monkey, has potential to be an animal model for drug metabolism studies. In this study, we identified and characterized cytochrome P450 (P450) 1A1 and 1B1 in addition to the known P450 1A2 in marmosets. Marmoset P450 1A1 and 1B1 cDNA contained open reading frames encoding 512 and 543 amino acids, respectively, with high sequence identities (90%-93%) to other primate P450 1A1s and 1B1s. A phylogenetic tree based on amino acid sequences showed close evolutionary relationships among marmoset, macaque, and human P450 1A and 1B enzymes. By mRNA quantification and immunoblot analyses in five marmoset tissues, P450 1A1 was mainly expressed in lungs and small intestines, and P450 1A2 was expressed predominantly in livers. In contrast, P450 1B1 was expressed in all tissues tested. Marmoset P450 1A1, 1A2, and 1B1 heterologously expressed in Escherichia coli catalyzed 7-ethoxyresorufin O-deethylation, 7-ethoxycoumarin O-deethylation, and phenacetin O-deethylation, similar to those of humans and cynomolgus monkeys. Notably, marmoset P450 1A1 and 1A2 more efficiently catalyzed 7-ethoxyresorufin O-deethylation than those of the human homologs, but were comparable to those of the cynomolgus monkey homologs. Additionally, marmoset P450 1B1 preferentially catalyzed estradiol 4-hydroxylation; however, rat P450 1B1 more favorably catalyzed estradiol 2-hydroxylation, indicating that the estradiol hydroxylation specificity of marmoset P450 1B1 was similar to those of human and cynomolgus monkey P450 1B1. These results indicated that marmoset P450 1A and 1B enzymes had functional characteristics similar to those of humans and cynomolgus monkeys, suggesting that P450 1A and 1B-dependent metabolism was similar among marmosets, cynomolgus monkeys, and humans.

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Overview of the marmoset as a model in nonclinical development of pharmaceutical products

Cited by 65 publications

References 82 publications

Small RNA profiling and characterization of piRNA clusters in the adult testes of the common marmoset, a model primate

Small RNA profiling and characterization of piRNA clusters in the adult testes of the common marmoset, a model primate

Isolation and characterization of a novel Helicobacter species, Helicobacter jaachi sp. nov., from common marmosets (Callithrix jaachus)

Molecular Cloning, Tissue Distribution, and Functional Characterization of Marmoset Cytochrome P450 1A1, 1A2, and 1B1

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