scholarly journals Survey of Drug Oxidation Activities in Hepatic and Intestinal Microsomes of Individual Common Marmosets, a New Nonhuman Primate Animal Model

2019 ◽  
Vol 20 (2) ◽  
pp. 103-113 ◽  
Author(s):  
Shotaro Uehara ◽  
Toru Oshio ◽  
Kazuyuki Nakanishi ◽  
Etsuko Tomioka ◽  
Miyu Suzuki ◽  
...  
Keyword(s):  
Animal Model ◽  
Nonhuman Primate ◽  
Molecular Mechanisms ◽  
Common Marmoset ◽  
Primate Species ◽  
Common Marmosets ◽  
Hepatic Microsomes ◽  
Model Animal ◽  
Intestinal Microsomes ◽  
Drug Oxidation

Background: Common marmosets (Callithrix jacchus) are potentially useful nonhuman primate models for preclinical studies. Information for major drug-metabolizing cytochrome P450 (P450) enzymes is now available that supports the use of this primate species as an animal model for drug development. Here, we collect and provide an overview of information on the activities of common marmoset hepatic and intestinal microsomes with respect to 28 typical human P450 probe oxidations. Results: Marmoset P450 2D6/8-dependent R-metoprolol O-demethylation activities in hepatic microsomes were significantly correlated with those of midazolam 1′- and 4-hydroxylations, testosterone 6β-hydroxylation, and progesterone 6β-hydroxylation, which are probe reactions for marmoset P450 3A4/5/90. In marmosets, the oxidation activities of hepatic microsomes and intestinal microsomes were roughly comparable for midazolam and terfenadine. Overall, multiple forms of marmoset P450 enzymes in livers and intestines had generally similar substrate recognition functionalities to those of human and/or cynomolgus monkey P450 enzymes. Conclusion: The marmoset could be a model animal for humans with respect to the first-pass extraction of terfenadine and related substrates. These findings provide a foundation for understanding individual pharmacokinetic and toxicological results in nonhuman primates as preclinical models and will help to further support understanding of the molecular mechanisms of human P450 function.

Antisera against Neisseria gonorrhoeae cross-react with specific brain proteins of the common marmoset monkey and other nonhuman primate species

2016 ◽  
Vol 1653 ◽  
pp. 23-38 ◽  
Author(s):  
Bernhard Reuss ◽  
Abdul R. Asif ◽  
Abdullah Almamy ◽  
Christian Schwerk ◽  
Horst Schroten ◽  
...  
Keyword(s):  
Neisseria Gonorrhoeae ◽  
Nonhuman Primate ◽  
Common Marmoset ◽  
Primate Species ◽  
Brain Proteins ◽  
Marmoset Monkey ◽  
The Common ◽  
Nonhuman Primate Species

scholarly journals DNA methylation age analysis of rapamycin in common marmosets

2020 ◽  
Author(s):  
Steve Horvath ◽  
Joseph A. Zoller ◽  
Amin Haghani ◽  
Ake T. Lu ◽  
Ken Raj ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Rhesus Macaques ◽  
Common Marmoset ◽  
Primate Species ◽  
Vervet Monkeys ◽  
Methylation Data ◽  
Common Marmosets ◽  
Biomarkers Of Aging ◽  
Epigenetic Age ◽  
The Common

AbstractHuman DNA methylation data have previously been used to develop highly accurate biomarkers of aging (“epigenetic clocks”). Subsequent studies demonstrate that similar epigenetic clocks can also be developed for mice and many other mammals. Here, we describe epigenetic clocks for common marmosets (Callithrix jacchus) based on novel DNA methylation data generated from highly conserved mammalian CpGs that were profiled using a custom Infinium array (HorvathMammalMethylChip40). From these, we developed and present here, two epigenetic clocks for marmosets that are applicable to whole blood samples. We find that the human-marmoset clock for relative age exhibits moderately high age correlations in two other non-human primate species: vervet monkeys and rhesus macaques. In a separate cohort of marmosets, we tested whether intervention with rapamycin, a drug shown to extend lifespan in mice, would alter the epigenetic age of marmosets, as measured by the marmoset epigenetic clocks. These clocks did not detect significant effects of rapamycin on the epigenetic age of marmoset blood. The common marmoset stands out from other mammals in that it is not possible to build accurate estimators of sex based on DNA methylation data: the accuracy of a random forest predictor of sex (66%) was substantially lower than that observed for other mammals (which is close to 100%). Overall, the epigenetic clocks developed here for the common marmoset are expected to be useful for age estimation of wild-born animals and for anti-aging studies in this species.

scholarly journals HIV-1 Adapts To Replicate in Cells Expressing Common Marmoset APOBEC3G and BST2

2015 ◽  
Vol 90 (2) ◽  
pp. 725-740 ◽  
Author(s):  
Alberto Fernández-Oliva ◽  
Andrés Finzi ◽  
Hillel Haim ◽  
Luis Menéndez-Arias ◽  
Joseph Sodroski ◽  
...  
Keyword(s):  
Animal Model ◽  
Cell Cultures ◽  
Mononuclear Cells ◽  
Cultured Cells ◽  
Common Marmoset ◽  
Viral Fitness ◽  
Viral Escape ◽  
Restriction Factors ◽  
Common Marmosets ◽  
Hiv 1

ABSTRACTPrevious studies have shown that a major block to HIV-1 replication in common marmosets operates at the level of viral entry and that this block can be overcome by adaptation of the virus in tissue-cultured cells. However, our current studies indicate that HIV-1 encounters additional postentry blocks in common marmoset peripheral blood mononuclear cells. Here, we show that the common marmoset APOBEC3G (A3G) and BST2 proteins block HIV-1 in cell cultures. Using a directed-evolution method that takes advantage of the natural ability of HIV-1 to mutate during replication, we have been able to overcome these blocks in tissue-cultured cells. In the adapted viruses, specific changes were observed ingag,vif,env, andnef. The contribution of these changes to virus replication in the presence of the A3G and BST2 restriction factors was studied. We found that certain amino acid changes in Vif and Env that arise during adaptation to marmoset A3G and BST2 allow the virus to replicate in the presence of these restriction factors. The changes in Vif reduce expression levels and encapsidation of marmoset APOBEC3G, while the changes in Env increase viral fitness and discretely favor cell-to-cell transmission of the virus, allowing viral escape from these restriction factors.IMPORTANCEHIV-1 can infect only humans and chimpanzees. The main reason for this narrow tropism is the presence in many species of dominant-acting factors, known as restriction factors, that block viral replication in a species-specific way. We have been exploring the blocks to HIV-1 in common marmosets, with the ultimate goal of developing a new animal model of HIV-1 infection in these monkeys. In this study, we observed that common marmoset APOBEC3G and BST2, two known restriction factors, are able to block HIV-1 in cell cultures. We have adapted HIV-1 to replicate in the presence of these restriction factors and have characterized the mechanisms of escape. These studies can help in the development of a novel animal model forin vivoinfection of marmosets with HIV-1-like viruses.

scholarly journals A platform for semi-automated voluntary training of common marmosets for behavioral neuroscience: Voluntary training of common marmosets

2019 ◽  
Author(s):  
Jeffrey D. Walker ◽  
Friederice Pirschel ◽  
Nicholas Gidmark ◽  
Jason N. MacLean ◽  
Nicholas G. Hatsopoulos
Keyword(s):  
Foraging Behavior ◽  
Upper Limb ◽  
Model Organism ◽  
Common Marmoset ◽  
Digital Fabrication ◽  
Behavioral Neuroscience ◽  
Primate Species ◽  
Behavioral Training ◽  
Common Marmosets ◽  
Cad Models

ABSTRACTIn most cases, behavioral neuroscience studies of the common marmoset employ adaptations of well-established methods used with macaque monkeys. However, in most cases these approaches do not readily generalize to marmosets indicating a need for alternatives. Here we present the development of one such alternate: a platform for semi-automated, voluntary in-home cage behavioral training that allows for the study of naturalistic behaviors. We describe the design and production of a modular behavioral training apparatus using CAD software and digital fabrication. We demonstrate that this apparatus permits voluntary behavioral training and data collection throughout the marmoset’s waking hours with little experimenter intervention. Further we demonstrate the use of this apparatus to reconstruct the kinematics of the marmoset’s upper limb movement during natural foraging behavior.NEW AND NOTEWORTHYThe study of marmosets in neuroscience has grown rapidly and this model organism presents challenges that are unique to this primate species. Here we address those challenges with an innovative platform for semi-automated and voluntary training of common marmosets. The platform allows marmosets to train throughout their waking hours with little to no experimenter intervention. We describe the use of this platform to capture the kinematics of the upper limb during natural foraging behavior and to expand the opportunities for behavioral training beyond the limits of traditional behavioral training sessions. The platform is flexible and can be easily extended to incorporate other motor tasks (e.g. visually cued reaching or manipulandum based tasks) using CAD models and digital fabrication.

scholarly journals DNA methylation age analysis of rapamycin in common marmosets

GeroScience ◽  
2021 ◽  
Author(s):  
Steve Horvath ◽  
Joseph A. Zoller ◽  
Amin Haghani ◽  
Ake T. Lu ◽  
Ken Raj ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Rhesus Macaques ◽  
Common Marmoset ◽  
Primate Species ◽  
Vervet Monkeys ◽  
Methylation Data ◽  
Common Marmosets ◽  
Biomarkers Of Aging ◽  
Epigenetic Age ◽  
The Common

AbstractHuman DNA methylation data have previously been used to develop highly accurate biomarkers of aging (“epigenetic clocks”). Subsequent studies demonstrate that similar epigenetic clocks can also be developed for mice and many other mammals. Here, we describe epigenetic clocks for common marmosets (Callithrix jacchus) based on novel DNA methylation data generated from highly conserved mammalian CpGs that were profiled using a custom Infinium array (HorvathMammalMethylChip40). From these, we developed and present here two epigenetic clocks for marmosets that are applicable to whole blood samples. We find that the human-marmoset clock for relative age exhibits moderately high age correlations in two other non-human primate species: vervet monkeys and rhesus macaques. In a separate cohort of marmosets, we tested whether intervention with rapamycin, a drug shown to extend lifespan in mice, would alter the epigenetic age of marmosets, as measured by the marmoset epigenetic clocks. These clocks did not detect significant effects of rapamycin on the epigenetic age of marmoset blood. The common marmoset stands out from other mammals in that it is not possible to build accurate estimators of sex based on DNA methylation data: the accuracy of a random forest predictor of sex (66%) was substantially lower than that observed for other mammals (which is close to 100%). Overall, the epigenetic clocks developed here for the common marmoset are expected to be useful for age estimation of wild-born animals and for anti-aging studies in this species.

scholarly journals GB virus B infection of the common marmoset (Callithrix jacchus) and associated liver pathology

2004 ◽  
Vol 85 (9) ◽  
pp. 2525-2533 ◽  
Author(s):  
James R. Jacob ◽  
Kuei-Chin Lin ◽  
Bud C. Tennant ◽  
Keith G. Mansfield
Keyword(s):  
Acute Hepatitis ◽  
New World ◽  
Antiviral Drug ◽  
Common Marmoset ◽  
Callithrix Jacchus ◽  
Primate Species ◽  
New World Primates ◽  
Common Marmosets ◽  
The Common ◽  
Human Primate

GB virus B (GBV-B) is a flavivirus that is related closely to hepatitis C virus (HCV) and induces an acute hepatitis when inoculated into several species of New World primates. Common marmosets (Callithrix jacchus) are a widely available, non-endangered primate species that is susceptible to GBV-B infection and develops a characteristic acute hepatitis. Here, animals were found to be susceptible to serially passaged serum and GBV-B transcripts. Hepatic pathology and peripheral viraemia could be quantified biochemically, immunophenotypically and morphologically, and persisted for periods of up to 6 months in some animals. Hepatitis was characterized by a marked influx of CD3+ CD8+ T lymphocytes and CD20+ B cells within the first 2 months of primary infection. The results of this study document the marmoset as another small, non-human primate species in which the pathogenesis of GBV-B can be studied and used as a surrogate model of HCV infection for investigation of pathogenesis and antiviral drug development.

scholarly journals Herpesvirus saimiri strain 11 immortalizes a restricted marmoset T8 lymphocyte subpopulation in vitro.

1986 ◽  
Vol 164 (3) ◽  
pp. 926-931 ◽  
Author(s):  
M Kiyotaki ◽  
R C Desrosiers ◽  
N L Letvin
Keyword(s):  
Cell Lines ◽  
New World ◽  
Cell Function ◽  
Nk Cell ◽  
Common Marmoset ◽  
Primate Species ◽  
Herpesvirus Saimiri ◽  
New World Monkeys ◽  
Common Marmosets

Herpesvirus saimiri induces a fatal lymphoproliferative syndrome in a variety of New World primate species. We now show that cell lines derived from PBL of the common marmoset by in vitro-immortalization with H. saimiri strain 11 represent a remarkably restricted lymphocyte population. These cell lines have NK cell function, phenotypically express both suppressor/cytotoxic (T8) and NK cell (NKH1)-associated antigens, and express a T cell receptor. This subpopulation of lymphocytes is a very minor population of cells in the peripheral blood of common marmosets (less than or equal to 3%). The specificity in the interaction between H. saimiri strain 11 and a subpopulation of common marmoset lymphocytes represents an example of a restricted viral lymphotropism and may have important implications for the disease induced by this virus in New World monkeys.

scholarly journals Differential expression of GLUT2 in pancreatic islets and kidneys of New and Old World nonhuman primates

2009 ◽  
Vol 296 (3) ◽  
pp. R786-R793 ◽  
Author(s):  
Joshua Kramer ◽  
Elisabeth Ludlage Moeller ◽  
Audra Hachey ◽  
Keith G. Mansfield ◽  
Lynn M. Wachtman
Keyword(s):  
Pancreatic Islets ◽  
Nonhuman Primate ◽  
New World ◽  
Nonhuman Primates ◽  
Glucose Transporter ◽  
Health Concern ◽  
Primate Species ◽  
New World Monkeys ◽  
Common Marmosets ◽  
Old World

Diabetes is a growing public health concern, and animal models of this disease are necessary for a full understanding of disease pathogenesis, progression, clinical sequelae, and treatment options. In particular, nonhuman primate models of diabetes are important because of their close genetic relationship to humans. Although numerous Old World primate models have been described, few studies have examined the possibility of using New World monkeys as an animal model for this disease. Streptozotocin (STZ) is a common diabetogenic drug that selectively destroys beta cells after uptake via the GLUT2 glucose transporter. Induction of diabetes using STZ was attempted in common marmosets ( Callithrix jacchus). These animals showed increases in blood glucose consistent with diabetes only at STZ doses markedly greater than those used in other primate species. Additionally, all animals showed pathological evidence of acute renal and liver toxicity secondary to the treatment. In a subsequent comparative study of various nonhuman primates, GLUT2 immunostaining in pancreatic islets was used as a marker for sensitivity to STZ. Immunostaining of islets from a variety of nonhuman primate species indicated a reduced expression of pancreatic GLUT2 in New compared with Old World monkeys; this finding explains their resistance to diabetic induction with STZ. Furthermore, there were age-dependent differences in GLUT2 expression, with aged and infant macaques showing reduced expression. We conclude that New World monkeys are an inappropriate model for diabetes induction with STZ and that, with all primate species, it is important to consider the animals’ age before diabetic induction with STZ is attempted.

Electron Microscopic Detection and Characterization of Nonhuman Primate Enteric Viruses

1982 ◽  
Vol 40 ◽  
pp. 306-307
Author(s):  
G. C. Smith ◽  
R. L. Heberling ◽  
S. S. Kalter
Keyword(s):  
Electron Microscopy ◽  
Animal Model ◽  
Nonhuman Primate ◽  
Clinical Condition ◽  
Intestinal Tract ◽  
Enteric Viruses ◽  
Electron Microscopic ◽  
Microscopic Detection

A number of viral agents are recognized as and suspected of causing the clinical condition “gastroenteritis.” In our attempts to establish an animal model for studies of this entity, we have been examining the nonhuman primate to ascertain what viruses may be found in the intestinal tract of “normal” animals as well as animals with diarrhea. Several virus types including coronavirus, adenovirus, herpesvirus, and picornavirus (Table I) were detected in our colony; however, rotavirus, astrovirus, and calicivirus have not yet been observed. Fecal specimens were prepared for electron microscopy by procedures reported previously.

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