Uterus allotransplantation in cynomolgus macaque: A preliminary experience with non-human primate models

Prion diseases are characterized by the prominent accumulation of the misfolded form of a normal cellular protein (PrPSc) in the central nervous system. The pathological features and biochemical properties of PrPSc in macaque monkeys infected with the bovine spongiform encephalopathy (BSE) prion have been found to be similar to those of human subjects with variant Creutzfeldt–Jakob disease (vCJD). Non-human primate models are thus ideally suited for performing valid diagnostic tests and determining the efficacy of potential therapeutic agents. In the current study, we developed a highly efficient method for in vitro amplification of cynomolgus macaque BSE PrPSc. This method involves amplifying PrPSc by protein misfolding cyclic amplification (PMCA) using mouse brain homogenate as a PrPC substrate in the presence of sulfated dextran compounds. This method is capable of amplifying very small amounts of PrPSc contained in the cerebrospinal fluid (CSF) and white blood cells (WBCs), as well as in the peripheral tissues of macaques that have been intracerebrally inoculated with the BSE prion. After clinical signs of the disease appeared in three macaques, we detected PrPSc in the CSF by serial PMCA, and the CSF levels of PrPSc tended to increase with disease progression. In addition, PrPSc was detectable in WBCs at the clinical phases of the disease in two of the three macaques. Thus, our highly sensitive, novel method may be useful for furthering the understanding of the tissue distribution of PrPSc in non-human primate models of CJD.

Download Full-text

Advancing the genetic utility of pre-clinical species through a high-quality assembly of the cynomolgus monkey (Macaca fascicularis) genome

10.1101/2020.05.01.072280 ◽

2020 ◽

Author(s):

Elias Oziolor ◽

Shawn Sullivan ◽

Hayley Mangelson ◽

Stephen M. Eacker ◽

Michael Agostino ◽

...

Keyword(s):

Biomedical Research ◽

Genetic Architecture ◽

Cynomolgus Macaque ◽

Hybrid Assembly ◽

Primate Model ◽

Sequencing Technologies ◽

Macaque Genome ◽

Long Read ◽

Demographic Estimation ◽

Human Primate

AbstractThe cynomolgus macaque is a non-human primate model, heavily used in biomedical research, but with outdated genomic resources. Here we have used the latest long-read sequencing technologies in order to assemble a fully phased, chromosome-level assembly for the cynomolgus macaque. We have built a hybrid assembly with PacBio, 10x Genomics, and HiC technologies, resulting in a diploid assembly that spans a length of 5.1 Gb with a total of 16,741 contigs (N50 of 0.86Mb) contained in 370 scaffolds (N50 of 138 Mb) positioned on 42 chromosomes (21 homologous pairs). This assembly is highly homologous to former assemblies and identifies novel inversions and provides higher confidence in the genetic architecture of the cynomolgus macaque genome. A demographic estimation is also able to capture the recent genetic bottleneck in the Mauritius population, from which the sequenced individual originates. We offer this resource as an enablement for genetic tools to be built around this important model for biomedical research.

Download Full-text

Chromosomal-scale De novo Genome Assemblies of Cynomolgus Macaque and Common Marmoset

10.1101/2020.12.04.411207 ◽

2020 ◽

Author(s):

Vasanthan Jayakumar ◽

Osamu Nishimura ◽

Mitsutaka Kadota ◽

Naoki Hirose ◽

Hiromi Sano ◽

...

Keyword(s):

Human Genome ◽

Biomedical Research ◽

De Novo ◽

Massively Parallel Sequencing ◽

Cynomolgus Macaque ◽

Common Marmoset ◽

Contact Maps ◽

Long Reads ◽

Genome Assemblies ◽

Human Primate

AbstractCynomolgus macaque (Macaca fascicularis) and common marmoset (Callithrix jacchus) have been widely used in human biomedical research. Their genomes were sequenced and assembled initially using short-read sequences, with the advent of massively parallel sequencing. However, the resulting contig sequences tended to remain fragmentary, and long-standing primate genome assemblies used the human genome as a reference for ordering and orienting the assembled fragments into chromosomes. Here we performed de novo genome assembly of these two species without any human genome-based bias observed in the genome assemblies released earlier. Firstly we assembled PacBio long reads, and the resultant contigs were scaffolded with Hi-C data. The scaffolded sequences obtained were further refined based on assembly results of alternate de novo assemblies and Hi-C contact maps by resolving identified inconsistencies. The final assemblies achieved N50 lengths of 149 Mb and 137 Mb for cynomolgus macaque and common marmoset, respectively, and the numbers of scaffolds longer than 10Mb are equal to their chromosome numbers. The high fidelity of our assembly is ascertained by concordance to the BAC-end read pairs observed for common marmoset, as well as a high resemblance of their karyotypic organization. Our assembly of cynomolgus macaque outperformed all the available assemblies of this species in terms of contiguity. The chromosome-scale genome assemblies produced in this study are valuable resources for non-human primate models and provide an important baseline in human biomedical research.

Download Full-text

Acute Radiation Effects, the H-ARS in the Non-human Primate: A Review and New Data for the Cynomolgus Macaque with Reference to the Rhesus Macaque

Health Physics ◽

10.1097/hp.0000000000001442 ◽

2021 ◽

Vol 121 (4) ◽

pp. 304-330 ◽

Cited By ~ 1

Author(s):

Ann M. Farese ◽

Michel Drouet ◽

Francis Herodin ◽

Jean-Marc Bertho ◽

Karla D. Thrall ◽

...

Keyword(s):

Rhesus Macaque ◽

Radiation Effects ◽

Cynomolgus Macaque ◽

Acute Radiation ◽

Human Primate

Download Full-text

Revised recommendations for health monitoring of non-human primate colonies (2018): FELASA Working Group Report

Laboratory Animals ◽

10.1177/0023677219844541 ◽

2019 ◽

Vol 53 (5) ◽

pp. 429-446 ◽

Cited By ~ 1

Author(s):

Ivan Balansard ◽

Lorna Cleverley ◽

Keith L Cutler ◽

Mats G Spångberg ◽

Kevin Thibault-Duprey ◽

...

Keyword(s):

Health Monitoring ◽

Cynomolgus Macaque ◽

Common Marmoset ◽

Saimiri Sciureus ◽

Improve Health Status ◽

Screening Strategies ◽

Biological Similarity ◽

Micro Organisms ◽

And Control ◽

Human Primate

The genetic and biological similarity between non-human primates and humans has ensured the continued use of primates in biomedical research where other species cannot be used. Health-monitoring programmes for non-human primates provide an approach to monitor and control both endemic and incoming agents that may cause zoonotic and anthroponotic disease or interfere with research outcomes. In 1999 FELASA recommendations were published which aimed to provide a harmonized approach to health monitoring programmes for non-human primates. Scientific and technological progress, understanding of non-human primates and evolving microbiology has necessitated a review and replacement of the current recommendations. These new recommendations are aimed at users and breeders of the commonly used non-human primates; Macaca mulatta (Rhesus macaque) and Macaca fascicularis (Cynomolgus macaque). In addition, other species including Callithrix jacchus (Common marmoset) Saimiri sciureus (Squirrel monkey) and others are included. The important and challenging aspects of non-human primate health-monitoring programmes are discussed, including management protocols to maintain and improve health status, health screening strategies and procedures, health reporting and certification. In addition, information is provided on specific micro-organisms and the recommended frequency of testing.

Download Full-text

Chromosomal-scale de novo genome assemblies of Cynomolgus Macaque and Common Marmoset

Scientific Data ◽

10.1038/s41597-021-00935-6 ◽

2021 ◽

Vol 8 (1) ◽

Author(s):

Vasanthan Jayakumar ◽

Osamu Nishimura ◽

Mitsutaka Kadota ◽

Naoki Hirose ◽

Hiromi Sano ◽

...

Keyword(s):

Human Genome ◽

Biomedical Research ◽

Macaca Fascicularis ◽

De Novo ◽

Cynomolgus Macaque ◽

Common Marmoset ◽

Contact Maps ◽

Long Reads ◽

Genome Assemblies ◽

Human Primate

AbstractCynomolgus macaque (Macaca fascicularis) and common marmoset (Callithrix jacchus) have been widely used in human biomedical research. Long-standing primate genome assemblies used the human genome as a reference for ordering and orienting the assembled fragments into chromosomes. Here we performed de novo genome assembly of these two species without any human genome-based bias observed in the genome assemblies released earlier. We assembled PacBio long reads, and the resultant contigs were scaffolded with Hi-C data, which were further refined based on Hi-C contact maps and alternate de novo assemblies. The assemblies achieved scaffold N50 lengths of 149 Mb and 137 Mb for cynomolgus macaque and common marmoset, respectively. The high fidelity of our assembly is also ascertained by BAC-end concordance in common marmoset. Our assembly of cynomolgus macaque outperformed all the available assemblies of this species in terms of contiguity. The chromosome-scale genome assemblies produced in this study are valuable resources for non-human primate models and provide an important baseline in human biomedical research.

Download Full-text

Macaca fascicularis papillomavirus type 1: a non-human primate betapapillomavirus causing rapidly progressive hand and foot papillomatosis

Journal of General Virology ◽

10.1099/vir.0.006544-0 ◽

2009 ◽

Vol 90 (4) ◽

pp. 987-994 ◽

Cited By ~ 15

Author(s):

Joongho Joh ◽

Kelly Hopper ◽

Koenraad Van Doorslaer ◽

John P. Sundberg ◽

Alfred B. Jenson ◽

...

Keyword(s):

Genomic Dna ◽

Macaca Fascicularis ◽

Cynomolgus Macaque ◽

Pcr Amplification ◽

Open Reading Frames ◽

Coding Region ◽

Primate Model ◽

Hands And Feet ◽

Human Primate

Papillomaviruses (PVs) are a group of small, non-enveloped DNA viruses that cause mucosal or cutaneous neoplasia in a variety of animals. Whilst most papillomas will regress spontaneously, some may persist or undergo malignant transformation. In this study, aggressive, persistent and extensive warts were observed on the hands and feet of a cynomolgus macaque (Macaca fascicularis). The presence of PV in the wart biopsies was identified by immunohistochemistry and PCR amplification of PV DNA. The genomic DNA of this PV was cloned and sequenced, and the PV was designated M. fascicularis papillomavirus type 1 (MfPV-1). Its genome was 7588 bp in length and the organization of its putative open reading frames (E1, E2, E6, E7, L1, L2 and E4) was similar to that of other PVs. MfPV-1 had a short non-coding region (NCR) of 412 bp. Molecular analysis of MfPV-1 genomic DNA classified it into the genus Betapapillomavirus, to which all epidermodysplasia verruciformis (EV)-type PVs belong. Diseases caused by PVs of the genus Betapapillomavirus are usually associated with natural or iatrogenic immunosuppression. The genomic characterization performed in this study showed that MfPV-1 clustered within the genus Betapapillomavirus and also contained EV-type-specific motifs in its NCR. Further characterization of this virus and its host interactions may allow us to develop a non-human primate model for human betapapillomaviruses, a genus populated by human PV types causing EV.

Download Full-text