Background pathology of the common marmoset (Callithrix jacchus) in toxicological studies

Kaspareit, J.; Friderichs-Gromoll, S.; Buse, Eberhard; Habermann, Gunnar

doi:10.1016/j.etp.2006.02.013

Cited by 44 publications

(48 citation statements)

References 14 publications

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“…This study extends and refines previously published observations of incidental findings in the thymus (Chamanza et al 2010;Ito et al 1992;Okazaki et al 1996;Kaspareit et al 2006;Spoor, Radi, and Dunstan 2008) by providing a detailed evaluation of the range of light microscopic observations correlated with thymus weight and maturity stage. We also conducted a review of selected immunomodulators to determine the relative sensitivity of thymus and spleen parameters.…”

Section: Introductionsupporting

confidence: 64%

Maturity-related Variability of the Thymus in Cynomolgus Monkeys (Macaca fascicularis)

et al. 2016

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Terminal body weights (TBWs), thymus weight parameters, and thymus morphology were retrospectively evaluated in 453 cynomolgus monkeys assigned to control groups on nonclinical toxicity studies. Morphology of bone, ovary, and testis/epididymis were used to determine maturity status of individual animals. There was no correlation between TBW and thymus weight (absolute and/or relative to TBW or brain weight). Thymus weight parameters and grades of decreased lymphocytes in the thymus were highly variable in immature animals compared to mature animals. There was also high (up to 11-fold) variability of thymus weight parameters within a given control group on the same study (generally 3 or 4 animals per sex). Several parameters evaluated had more pronounced age-related changes in males when compared to females. Our results demonstrate the inherent variability of thymus weight parameters and morphologic observations for cynomolgus monkeys on toxicology studies. Changes in thymus parameters in cynomolgus monkeys are unreliable indicators of immunomodulation or immunotoxicity in the absence of other relevant findings. Therefore, the thymus parameters commonly evaluated in preclinical safety assessments should not be the primary data set used to determine the presence of a direct test article-related effect on the immune system.

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Section: Introductionsupporting

confidence: 64%

Maturity-related Variability of the Thymus in Cynomolgus Monkeys (Macaca fascicularis)

et al. 2016

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“…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 marmosets (Chalmers et al, 1983;David et al, 2009;Kaspareit et al, 2006;Ludlage et al, 2005) Abbreviations: EHS, enterohepatic Helicobacter species; IBD, inflammatory bowel disease.…”

Section: Introductionsupporting

confidence: 67%

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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“…26,98 In cottoneared marmosets, apparent ''spontaneous'' EMH was found in mesenteric lymph nodes, spleen, liver, kidney, adrenal gland, and cerebral choroid plexus. 46,80 Marmosets and African hedgehogs (Atelerix albiventris) with a variety of underlying disorders also develop EMH in many tissues. 46,80,88 Of 14 African hedgehogs, 13 (91%) had splenic hematopoiesis at necropsy, regardless of the underlying condition.…”

Section: Activation Of Stem Cell Niches In Extramedullary Sitesmentioning

confidence: 99%

“…46,80 Marmosets and African hedgehogs (Atelerix albiventris) with a variety of underlying disorders also develop EMH in many tissues. 46,80,88 Of 14 African hedgehogs, 13 (91%) had splenic hematopoiesis at necropsy, regardless of the underlying condition. 87 The marmoset, tree shrew, and lesser hedgehog tenrec are important laboratory animal models such that future research using these species might help shed light on underlying mechanisms of EMH.…”

Section: Activation Of Stem Cell Niches In Extramedullary Sitesmentioning

confidence: 99%

Extramedullary Hematopoiesis: A New Look at the Underlying Stem Cell Niche, Theories of Development, and Occurrence in Animals

2012

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Extramedullary hematopoiesis (EMH) is the formation and development of blood cells outside the medullary spaces of the bone marrow. Although widely considered an epiphenomenon, secondary to underlying primary disease and lacking serious clinical or diagnostic implications, the presence of EMH is far from incidental on a molecular basis; rather, it reflects a well-choreographed suite of changes involving stem cells and their microenvironment (the stem cell niche). The goals of this review are to reconsider the molecular basis of EMH based on current knowledge of stem cell niches and to examine its role in the pathophysiologic mechanisms of EMH in animals. The ability of blood cells to home, proliferate, and mature in extramedullary tissues of adult animals reflects embryonic patterns of hematopoiesis and establishment or reactivation of a stem cell niche. This involves pathophysiologic alterations in hematopoietic stem cells, extracellular matrix, stromal cells, and local and systemic chemokines. Four major theories involving changes in stem cells and/or their microenvironment can explain the development of most occurrences of EMH: (1) severe bone marrow failure; (2) myelostimulation; (3) tissue inflammation, injury, and repair; and (4) abnormal chemokine production. EMH has also been reported within many types of neoplasms. Understanding the concepts and factors involved in stem cell niches enhances our understanding of the occurrence of EMH in animals and its relationship to underlying disease. In turn, a better understanding of the prevalence and distribution of EMH in animals and its molecular basis could further inform our understanding of the hematopoietic stem cell niche.

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Background pathology of the common marmoset (Callithrix jacchus) in toxicological studies

Cited by 44 publications

References 14 publications

Maturity-related Variability of the Thymus in Cynomolgus Monkeys (Macaca fascicularis)

Maturity-related Variability of the Thymus in Cynomolgus Monkeys (Macaca fascicularis)

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

Extramedullary Hematopoiesis: A New Look at the Underlying Stem Cell Niche, Theories of Development, and Occurrence in Animals

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