Aquaporin (AQP) is a water channel protein that is of critical importance in the urinary concentrating process and the regulation of water balance in the kidney, and at least seven AQPs are expressed at distinct sites in the kidney. The common marmoset monkey is widely used as an experimental animal included in the primate order in the filed of renal system. However, nothing is known about the expression AQP in the common marmoset monkey kidney. The purpose of this study was to establish the distribution of AQP-1, AQP-2, AQP-3 and AQP-4 in the common marmoset monkey kidney. We used three male common marmoset monkeys (Callithrix jacchus) ranging in age from 2 to 3 years. AQP-1 was expressed in segments 1, 2 and 3 of the proximal tubule, particularly abundant in segment 1, and also observed in the descending thin limb of the medulla. AQP-2 immunoreactivity was observed in the apical plasma membrane of principal cells in the cortical and medullary collecting ducts. AQP-3 immunostaining was intense in the basolateral plasma membrane of connecting tubules as well as in the cortical and outer medullary collecting ducts. AQP-4 was expressed mainly in the cytoplasm of inner medullary collecting duct cells. These data suggest that AQPs of the common marmoset monkey kidney may play a similar role in urinary concentrating processes and the regulation of water balance to that of AQPs in rats, mice and humans.
Animals ; Aquaporins* ; Callithrix* ; Cell Membrane ; Cytoplasm ; Extremities ; Haplorhini* ; Humans ; Immunohistochemistry ; Kidney* ; Male ; Mice ; Primates ; Rats

Nonhuman primates (NHPs) have been widely used in reproductive biology, neuroscience, and drug development since a number of primate species are phylogenetically close to humans. In this review, we summarize the use of NHPs for nonclinical application in the reproductive system disorders including the loss or failure of an organ or tissue. Causes of infertility include congenital aplasia and acquired disorders of the reproductive organs. In addition, anti-cancer treatments can deplete ovarian follicles, leading to premature ovarian failure, infertility and long-term health risks. Along with a limited supply of human reproductive organs, anatomic/physiologic similarities to humans support the need for NHP models (New-World monkeys such as the common marmoset and Old-World monkeys such as cynomolgus and rhesus monkeys) to promote the advances in female infertility studies. For maintaining and executing animal studies using NHP, special protocols including animal care, anesthetic protocol, surgical technique, and immunosuppressive protocol are necessary. With a growing interest in the potential therapies such as endometrial tissue engineering, and ovary/follicle cryopreservation and grafting in Korea, this review can be useful in selecting appropriate animal models and can bridge between nonclinical studies and clinical applications by providing detailed information on the use of NHPs in the field of reproductive organ disorders.
Animals ; Biology ; Callithrix ; Cryopreservation ; Female* ; Haplorhini ; Humans ; Infertility ; Infertility, Female ; Korea ; Models, Animal ; Neurosciences ; Ovarian Follicle ; Primary Ovarian Insufficiency ; Primates* ; Tissue Engineering ; Transplantation ; Transplants

The common marmoset (Callithrix jacchus) is a small-bodied, popular New World monkey and is used widely in reproductive biology, neuroscience, and drug development, due to its comparative ease of handling, high reproductive efficiency, and its unique behavioral characters. In this review, we discuss the marmoset models in Parkinson's disease (PD), which is a neurological movement disorder primarily resulting from a degeneration of dopaminergic neurons with clinical features of tremor, rigidity, postural instability, and akinesia. The most common PD models involve the administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) or 6-hydroxydopamine to study the pathogenesis and to evaluate novel therapies. Following the systemic or local administration of these neurotoxins, the marmosets with very severe Parkinson's symptoms are recommended to be placed in an intensive care unit with artificial feeding to increase survival rate. All procedures with MPTP should be conducted in a special room with enclosed cages under negative-pressure by trained researchers with personal protection. Behavioral tests are conducted to provide an external measure of the brain pathology. Along with several biomarkers, including alpha-synuclein and DJ-1, non-invasive neuroimaging techniques such as positron emission tomography and magnetic resonance imaging are used to evaluate the functional changes associated with PD. With the recent growing interest in potential and novel therapies such as stem cell and gene therapy for PD in Korea, the marmoset can be considered as a suitable non-human primate model in PD research to bridge the gap between rodent studies and clinical applications.
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine ; alpha-Synuclein ; Animals* ; Biomarkers ; Biology ; Brain Diseases ; Callithrix* ; Dopaminergic Neurons ; Genetic Therapy ; Humans ; Intensive Care Units ; Korea ; Magnetic Resonance Imaging ; Methods* ; Models, Animal ; Movement Disorders ; Neuroimaging ; Neurosciences ; Neurotoxins ; Nutritional Support ; Oxidopamine ; Parkinson Disease* ; Platyrrhini ; Positron-Emission Tomography ; Primates ; Rodentia ; Stem Cells ; Survival Rate ; Tremor

Stem cell technologies are particularly attractive in Parkinson's disease (PD) research although they occasionally need long-term treatment for anti-parkinsonian activity. Unfortunately, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) widely used as a model for PD has several limitations, including the risk of dose-dependent mortality and the difficulty of maintenance of PD symptoms during the whole experiment period. Therefore, we tested if our novel MPTP regimen protocol (2 mg/kg for 2 consecutive days and 1 mg/kg for next 3 consecutive days) can be maintained stable parkinsonism without mortality for long-term stem cell therapy. For this, we used small-bodied common marmoset monkeys (Callithrix jacchus) among several nonhuman primates showing high anatomical, functional, and behavioral similarities to humans. Along with no mortality, the behavioral changes involved in PD symptoms were maintained for 32 weeks. Also, the loss of jumping ability of the MPTP-treated marmosets in the Tower test was not recovered by 32 weeks. Positron emission tomography (PET) analysis revealed that remarkable decreases of bindings of ¹⁸F-FP-CIT were observed at the striatum of the brains of the marmosets received MPTP during the full period of the experiment for 32 weeks. In the substantia nigra of the marmosets, the loss of tyrosine hydroxylase (TH) immunoreactivity was also observed at 32 weeks following the MPTP treatment. In conclusion, our low-dose MPTP regimen protocol was found to be stable parkinsonism without mortality as evidenced by behavior, PET, and TH immunohistochemistry. This result will be useful for evaluation of possible long-term stem cell therapy for anti-parkinsonian activity.
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine* ; Brain ; Callithrix* ; Haplorhini ; Humans ; Immunohistochemistry ; Models, Animal ; Mortality ; Parkinson Disease* ; Parkinsonian Disorders ; Positron-Emission Tomography ; Primates ; Stem Cells* ; Substantia Nigra ; Tyrosine 3-Monooxygenase

Most of the endogenous retroviral genes integrated into the primate genome after the split of New World monkeys in the Oligocene era, approximately 33 million years ago. Because they can change the structure of adjacent genes and move between and within chromosomes they may play important roles in evolutionas well as in many kinds of disease and the creation of genetic polymorphism. Comparative analysis of HERVs (human endogenous retroviruses) and their LTR (long terminal repeat) elements in the primate genomes will help us to understand the possible impact of HERV elements in the evolution and phylogeny of primates. For example, HERV-K LTR and SINE-R elements have been identified that have been subject to recent change in the course of primate evolution. They are specific elements to the human genome and could be related to biological function. The HERV-M element is related to the superfamily of HERV-K and is integrated into the periphilin gene as the truncated form, 5'LTR-gag-pol-3'LTR. PCR and RT-PCR approaches indicated that the insertion of various retrotransposable elements in a common ancestor genome may make different transcript variants in different primate species. Examination of the HERV-W elementrevealed that env fragments were detected on human chromosomes 1, 3-7, 12, 14, 17, 20, and X, whilst the pol fragments were detected on human chromosomes 2-8, 10-15, 20, 21, X, and Y. Bioinformatic blast search showed that almost full-length of the HERV-W family was identified on human chromosomes 1-8, 11-15, 17, 18, 21, and X. Expression analysis of HERV-W genes (gag, pol, and env) in human tissues by RT-PCR indicated that gag and pol were expressed in specific tissues, whilst env was constituitively expressed in all tissues examined. DNA sequence based phylogenetic analysis indicated that the gag, pol and env genes have evolved independently during primate evolution. It will thus be of considerable interest to expand the current HERV gene information of various primates and disease tissues.
Base Sequence ; Chromosomes, Human ; Endogenous Retroviruses ; Genes, env ; Genome ; Genome, Human ; Humans* ; Phylogeny ; Platyrrhini ; Polymerase Chain Reaction ; Polymorphism, Genetic ; Primates ; Retroelements* ; Zidovudine

This study was performed to investigate the expression of two porcine endogenous retrovirus (PERV) elements, PERV gag and full-length conserved PERV, in blood cells collected periodically from organ-recipient monkeys that underwent pig to non-human primate xenotransplantation. The heart and kidney-respectively acquired from alpha-1,3-galactosyltransferase knockout (GT-KO) pigs that survived for24 and 25 days-were xenografted into cynomolgus monkeys. The two PERV elements expressed in the xenografted GT-KO pig organs were not present in the blood cells of the recipient monkeys. In the present study, we deduced that PERVs are not transmitted during GT-KO pig to monkey xenotransplantation.
Blood Cells ; Endogenous Retroviruses* ; Haplorhini* ; Heart ; Heterografts ; Macaca fascicularis ; Primates ; Swine ; Transplantation, Heterologous*

The organization of the striatal projection fibers from the hippocampal formation (HF) was studied in the monkey with particular emphasis on specific projections of the ventral striatum. Retrograde tracers were injected into the five different regions of the ventral striatum such as the ventromedial caudate nucleus, ventral shell, central shell, and dorsal core of the nucleus accumbens (NA), and ventrolateral putamen. The ventromedial caudate nucleus and the shell of the NA received dense projections from the HF. Although the ventromedial caudate nucleus and the shell of the NA are both innervated by the HF, the shell receives the larger of these projections. This suggests that the HF is more strongly connected with the shell of the NA than with the ventromedial caudate nucleus. There are no differences between the ventral shell and central shell of the NA. Labeled neurons were mainly observed in the rostral parts of the dorsomedial CA1 and adjacent subicular complex (prosubiculum, subiculum, presubiculum, and parasubiculum) of the HF. These results suggest that the shell of the NA is the main converging site receiving hippocampal projections primarily related to integrating visuospatial and limbic information.
Basal Ganglia* ; Caudate Nucleus ; Haplorhini ; Hippocampus ; Neurons ; Nucleus Accumbens ; Primates* ; Putamen

Microorganisms play important roles in obesity; however, the role of the gut microbiomes in obesity is controversial because of the inconsistent findings. This study investigated the gut microbiome communities in obese and lean groups of captive healthy cynomolgus monkeys reared under strict identical environmental conditions, including their diet. No significant differences in the relative abundance of Firmicutes, Bacteroidetes and Prevotella were observed between the obese and lean groups, but a significant difference in Spirochetes (p < 0.05) was noted. Microbial diversity and richness were similar, but highly variable results in microbial composition, diversity, and richness were observed in individuals, irrespective of their state of obesity. Distinct clustering between the groups was not observed by principal coordinate analysis using an unweighted pair group method. Higher sharedness values (95.81% ± 2.28% at the genus level, and 79.54% ± 5.88% at the species level) were identified among individual monkeys. This paper reports the association between the gut microbiome and obesity in captive non-human primate models reared under controlled environments. The relative proportion of Firmicutes and Bacteroidetes as well as the microbial diversity known to affect obesity were similar in the obese and lean groups of monkeys reared under identical conditions. Therefore, obesity-associated microbial changes reported previously appear to be associated directly with environmental factors, particularly diet, rather than obesity.
Bacteroidetes ; Diet ; Environment, Controlled ; Firmicutes ; Gastrointestinal Microbiome ; Haplorhini ; Macaca fascicularis ; Methods ; Microbiota ; Obesity ; Prevotella ; Primates ; Spirochaetales

Transplantation of the pancreas islet cell has been demonstrated to be able to cure for type I diabetes. It can offer not only discontinuing of insulin but also preventing of complications from diabetes. Islet cell transplantation has been very successful in small animals, but it is still unsuccessful in large animal, especially in non-human primate. Non-human primate trial has a value as a preclinical model prior to human application because of its close phylogenetic relationship to human. PURPOSE: The aim of this study is to develop the constant isolation method for obtaining sufficient number of islet in non-human primate pancreas to allow the human clinical islet transplantation more feasibly. METHODS: Ten pancreas were procured from cynomolgus (Macaca fasicularis) monkey. Islet isolation was done with the modified Ricordi's method using the new brand enzyme Liberase HI. Quantitaion of islet, viability staining insulin release without or with glucose stimulation, intracellular insulin content, DNA assay and in vivo transplantation into diabetic nude mice were done for quality control of islets. RESULTS: 2760 IEQ/pancreas gram with 91% of purity were able to be obtained by this isolation method using the new enzyme Liberase HI. These islets showed good quality of function, which demonstrated by in vitro standard assays. Euglycemia were achieved in 90% of streptozotocin induced diabetic nude mice by transplantation the purified islets (2,000 IEQ) into the subrenal space. CONCLUSION: Sufficient number of islets could be obtained from non-human primate through our method, and islets were able to respond glucose challenge and to eliminate the diabetes in streptozotocin induced diabetic nude mice. This implies we will be able to use this method as a preclinical model for human application for islet transplantation.
Animals ; DNA ; Glucose ; Haplorhini ; Humans* ; Insulin ; Islets of Langerhans ; Islets of Langerhans Transplantation ; Mice ; Mice, Nude ; Pancreas* ; Primates* ; Quality Control ; Streptozocin

Cynomolgus monkeys as nonhuman primates are valuable animal models because they have a high level of human gene homology. There are many reference values for hematology and biochemistry of Cynomolgus monkeys that are needed for proper clinical diagnosis and biomedical research conduct. The body weight information and blood type are also key success factors in allogeneic or xenogeneic models. Moreover, the biological parameters could be different according to the origin of the Cynomolgus monkey. However, there are limited references provided, especially of Cambodia origin. In this study, we measured average body weight of 2,518 Cynomolgus monkeys and analyzed hematology and serum biochemistry using 119 males, and determined blood types in 642 monkeys with Cambodia origin. The average body weight of male Cynomolgus monkeys were 2.56±0.345 kg and female group was 2.43±0.330 kg at the age from 2 to 3 years. The male group showed relatively sharp increased average body weight from the 3 to 4 age period compared to the female group. In hematology and biochemistry, it was found that most of the data was similar when compared to other references even though some results showed differences. The ABO blood type result showed that type A, B, AB, and O was approximately 15.6, 33.3, 44.2, and 6.9%, respectively. The main blood type in this facility was B and AB. These biological background references of Cambodia origin could be used to provide important information to researchers who are using them in their biomedical research.
Biochemistry* ; Body Weight ; Cambodia* ; Diagnosis ; Female ; Haplorhini ; Hematology* ; Humans ; Macaca fascicularis* ; Male ; Models, Animal ; Primates ; Reference Values*