Multiple transcription start sites for the GnRH gene in rhesus and cynomolgus monkeys: a non-human primate model for studying GnRH gene regulation

Abstract Social status is a powerful correlate of aging-related health decline. Observational data in humans suggest that disadvantaged social status may be associated with accelerated biological aging. But establishing causality in this relationship poses challenges; experimental manipulation of human social status is not possible. In contrast, social status can be experimentally manipulated non-human primates (e.g. Snyder-Mackler 2016 Science). We conducted analysis to reverse-translate blood-chemistry of biological aging to cynomolgus monkeys using data from several hundred animals in the Wake Primate Center breeding colony. We are applying these measures in an independent sample of monkeys with ascertained dominance rank to test replication in the non-human primate model of the human social gradient in biological aging. Parallel analysis of DNA methylation-based measures of biological aging are ongoing and should be available to present by Fall 2019. Results will inform potential to use this non-human primate model to study social determinants of biological aging.

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A new and spontaneous animal model for ankylosing spondylitis is found in cynomolgus monkeys

10.21203/rs.3.rs-25995/v1 ◽

2020 ◽

Author(s):

Huanhuan JIA ◽

Meili CHEN ◽

Xiaoling LUO ◽

Gang HOU ◽

Ting LUO ◽

...

Keyword(s):

Ankylosing Spondylitis ◽

Bone Formation ◽

Disease Progression ◽

Joint Disease ◽

Pathological Examination ◽

Radiographic Examination ◽

Primate Model ◽

Cynomolgus Monkeys ◽

Abnormal Movements ◽

Human Primate

Abstract Background Ankylosing spondylitis (AS) is a progressive, disabling joint disease that affects millions worldwide. There is a lack of useful disease model to conduct comprehensive mechanistic studies. Non-human primate model is a potential spontaneous model for ankylosing spondylitis (AS). Methods A group of cynomolgus monkeys with abnormal joints and abnormal movements were screened out from about 20,000 cynomolgus monkeys primarily. A 2-years follow-up study of this group of cynomolgus monkeys having joint lesions reported of spinal stiffness was performed by conducting hematological testing, radiographic examination, family aggregation analysis, pathological analysis and genetic testing. Results These diseased animals suffered from spontaneous AS with clinical features recapitulating human AS disease progression. The spontaneous incidence rate and the onset age of AS in monkeys similar to epidemiological features of AS patients. The disease progression in disease monkeys have shown bone erosion, osteophyte formation and “Bamboo-like” change. ESR, CRP IL-17, TNF-α and VEGF levels significantly increase in AS monkeys comparing with normal monkeys. Several features similar to AS patients, including cartilage destruction, cartilage ossification, chondroid metaplasia and bone formation were shown in AS monkeys pathological examination results. Both the serum bone resorption and bone formation biomarkers of AS monkeys were significantly reduce. In our current SNP sequencing results, loci that similar to AS-relative SNPs in human genome have not yet been found. Conclusions The study offers a promising non-human primate model for spontaneous ankylosing spondylitis which may serve as an excellent substitute for its pre-clinical research.

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Chronic unpredictable mild stress produces depressive-like behavior, hypercortisolemia, and metabolic dysfunction in adolescent cynomolgus monkeys

Translational Psychiatry ◽

10.1038/s41398-020-01132-6 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Teng Teng ◽

Carol A. Shively ◽

Xuemei Li ◽

Xiaofeng Jiang ◽

Gretchen N. Neigh ◽

...

Keyword(s):

Adolescent Depression ◽

Mild Stress ◽

Matched Pairs ◽

Metabolic Dysfunction ◽

Chronic Unpredictable Mild Stress ◽

Hair Cortisol ◽

Nonhuman Primate Model ◽

Primate Model ◽

Cynomolgus Monkeys ◽

Human Primate

AbstractAdolescent depression is a common and serious mental disorder with unique characteristics that are distinct from adult depression. The adult non-human primate stress-induced model of depressive-like behavior is an excellent model for the study of mechanisms; however, an adolescent nonhuman primate model is still lacking. Ten male adolescent cynomolgus monkeys were divided into a chronic unpredictable mild stress (CUMS, n = 5) group and a control (CON, n = 5) group by age and weight-matched pairs. The CUMS group was exposed to multiple unpredictable mild stressors for five cycles over 55 days. At baseline, there were no differences between CUMS and CON groups. At endpoint, the CUMS group demonstrated significantly higher depressive-like behavior (huddle posture), and significantly lower locomotion compared with the CON group. Furthermore, depressive-like behavior increased from baseline to endpoint in the CUMS group, but not changed in the CON group. In the attempt for apple test, the CUMS group made significantly fewer attempts for the apple than the CON group. In the human intruder test, the CUMS group showed significantly higher anxiety-like behaviors in the stare phase than the CON group. Hair cortisol level was significantly higher in the CUMS group than the CON group at endpoint, and was also elevated from baseline to endpoint. Metabolic profiling of plasma at endpoint identified alterations in metabolite pathways which overlapped with those of adolescent depression patients. CUMS can induce depressive-like and anxiety-like behaviors, hypercortisolemia, and metabolic perturbations in adolescent cynomolgus monkeys. This is a promising model to study the mechanisms underlying adolescent depression.

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Abstract 4950: Infection with Enterovirus Produces Myocarditis in a Non-Human Primate Model

Circulation ◽

10.1161/circ.118.suppl_18.s_963 ◽

2008 ◽

Vol 118 (suppl_18) ◽

Author(s):

Nancy Halnon ◽

Cheryl Cammock ◽

Morgan Singletary ◽

James Blanchard ◽

Jill Skoczylas ◽

...

Keyword(s):

Cardiac Tissue ◽

Cardiac Injury ◽

Clinical Specimen ◽

Neutralizing Antibody ◽

Primate Model ◽

Cynomolgus Monkeys ◽

Enteroviral Infection ◽

Antibody Titers ◽

Eosinophilic Myocarditis ◽

Human Primate

Introduction: We performed a pilot study to establish a non-human primate model of enteroviral infection and myocarditis. Methods: Juvenile cynomolgus monkeys were inoculated via oral (n=1) or intravenous (n=8) routes with a cloned Coxsackievirus B3 (CVB-3) or a CVB-3 /Enterovirus 86 strain (CVB-MCH) isolated from a clinical specimen from a patient with fatal myocarditis. Clinical and echocardiographic assessment was performed at baseline and at days 3, 7, 14, and 28. CVB-3 neutralizing antibody titers were measured. Viral RNA was detected by RT-PCR and culture of plasma and cardiac tissue. Animals were sacrificed at 14 or 28 days and myocardium examined for viral pathology. Results: Infection was achieved by both routes with both CVB-3 strains. Viremia was detected in 6/9, resolving after day 3. All (9/9) generated neutralizing antibody. Two animals infected with 10 7 infectious units (IU) of CVB-3 became moribund and were sacrificed at day 11 and day 14. Subsequent animals received 10 6 IU of CVB-3 and appeared well until sacrificed at day 14 (n=3) or day 28 (n=1). Three infected with 10 6 IU CVB-MCH also appeared well until sacrificed at day 28. Normal ejection fraction was maintained, but four animals had minor wall motion abnormalities. Serum troponin remained normal. Virus was present in myocardium in 5/5 tested. Multiple areas of focal cardiac injury were present in all animals and included lymphocytic or eosinophilic myocarditis (n=6), focal inflammation (n= 3), myocytolysis (n=2), ischemic foci (n=4), contraction band necrosis (n=2), and hypertrophy (n=3). Active myocarditis was present in 4/5 animals at day 14 and 2/4 at day 28. Conclusions: We were able to consistently establish infection with CVB-3 in cynomolgus monkeys resulting in clinically apparent or sub clinical disease, including myocarditis or cardiac injury persisting at 28 days. Despite adequate immune responses to clear viremia, virus persisted in the myocardium. The presence of myocyte hypertrophy and injury at 28 days in this model may provide a basis for experiments aimed at modulating immune or virus induced cardiomyopathy.

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Changes in transcription start sites of Zap1‐regulated genes during zinc deficiency: Implications for HNT1 gene regulation

Molecular Microbiology ◽

10.1111/mmi.14416 ◽

2019 ◽

Vol 113 (1) ◽

pp. 285-296

Author(s):

Supinda Tatip ◽

Janet Taggart ◽

Yirong Wang ◽

Colin W. MacDiarmid ◽

David J. Eide

Keyword(s):

Gene Regulation ◽

Zinc Deficiency ◽

Transcription Start ◽

Transcription Start Sites

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Multi-omics reveals principles of gene regulation and pervasive non-productive transcription in the human cytomegalovirus genome

10.1101/2022.01.07.472583 ◽

2022 ◽

Author(s):

Christopher Sebastian Jürges ◽

Manivel Lodha ◽

Vu Thuy Khanh Le-Trilling ◽

Pranjali Bhandare ◽

Elmar Wolf ◽

...

Keyword(s):

Gene Regulation ◽

Human Cytomegalovirus ◽

Viral Protein ◽

Transcription Initiation ◽

Molecular Mechanisms ◽

Viral Gene ◽

Transcription Start ◽

Reading Frame ◽

Transcription Start Sites ◽

Rna Labeling

For decades, human cytomegalovirus (HCMV) was thought to express ≈200 viral proteins during lytic infection. In recent years, systems biology approaches uncovered hundreds of additional viral gene products and suggested thousands of viral sites of transcription initiation. Despite all available data, the molecular mechanisms of HCMV gene regulation remain poorly understood. Here, we provide a unifying model of productive HCMV gene expression employing transcription start site profiling combined with metabolic RNA labeling as well as integrative computational analysis of previously published big data. This approach defined the expression of >2,600 high confidence viral transcripts and explained the complex kinetics of viral protein expression by cumulative effects of translation of incoming virion-associated RNA, multiple transcription start sites with distinct kinetics per viral open reading frame, and differences in viral protein stability. Most importantly, we identify pervasive transcription of transient RNAs as a common feature of this large DNA virus with its human host.

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Hexachlorobenzene toxicity in the monkey ovary: III. Ultrastructure induced by high (10 mg/kg) dose exposure

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100084958 ◽

1991 ◽

Vol 49 ◽

pp. 130-131

Author(s):

A. Singh ◽

A. Dykeman ◽

J. Jarrelf ◽

D. C. Villeneuve

Keyword(s):

Present Report ◽

Reproductive Toxicity ◽

Control Group ◽

Primate Model ◽

Human Follicular Fluid ◽

Thin Sections ◽

Cynomolgus Monkeys ◽

Cacodylate Buffer ◽

Induction Cycle ◽

Comprehensive Study

Hexachlorobenzene (HCB), a persistent and mobile organochlorine pesticide, occurs in environment. HCB has been shown to be present in human follicular fluid. An objective of the present report, which is part of a comprehensive study on reproductive toxicity of HCB, was to determine the cytologic effects of the compound on ovarian follicles in a primate model.Materials and Methods. Eight Cynomolgus monkeys were housed under controlled conditions at Animal facility of Health and Welfare, Ottawa. Animals were orally administered gelatin capsules containing HCB mixed with glucose in daily dosages of 0.0 or 10 mg/kg b.w. for 90 days; the former was the control group. On the menstrual period following completion of dosing, the monkeys underwent an induction cycle of superovulation. At necropsy, one-half of an ovary from each animal was diced into ca. 2- to 3-mm cubed specimens that were fixed by immersion in 2.5% glutaraldehyde in 0.1 M cacodylate buffer (pH 7.3). Subsequent procedures followed to obtain thin sections that were examined in a Hitachi H-7000 electron microscope have been described earlier.

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