The goal of this project is to expand the production of genetically characterized rhesus macaques that are specific pathogen free (SPF) for an extended list of persistent viruses, including simian immunodeficiency virus (SIV), simian T-lymphotropic virus (STLV), simian type D retrovirus (SRV-D), simian foamy virus (SFV), Cercopithecine herpesvirus I (B virus), rhesus cytomegalovirus (RhCMV), and rhesus rhadinovirus (RRV). This expansion will be geared to the production of SPF animals for use in AIDS-related and other NIH-funded research, and to establishing a long-term SPF breeding colony of rhesus macaques with known pedigrees and well-defined major histocompatability complex (MHC) genotypes. To meet these objectives, the investigators will derive SPF offspring from conventional non-SPF rhesus breeding stock of Chinese origin. An expanded program of MHC typing will be used to characterize breeding stock and offspring that will include additional microsatellite loci, class I alleles and class II genes. This expanded MHC typing will facilitate the identification and definition of immune response genotypes, and will allow for selected breeding to produce animals with specific genetic profiles in response to shifting research needs. Data generated by these studies will also allow the investigators to determine whether significant differences in MHC haplotype frequencies (which could reflect differences in immune response) exist between Chinese origin and Indian origin rhesus macaques. The determination and confirmation of B virus status has proven to be one of the most problematic aspects of SPF colony development. Augmented B virus screening utilizing polymerase chain reaction detection of viral shedding and in vitro assessment of cell-mediated immune responses to B virus antigens will be implemented for B virus surveillance. These studies will provide information on aspects of the natural history of B virus critical to the sound management and continued integrity of SPF macaque colonies. As the number of animals involved in SPF programs increases and the list of specific pathogens expands, there is a need for increased efficiency and cost-effectiveness of methods used for large-scale screening. To address this need, the investigators will optimize and validate a multiplex system for sero-detection of antibodies to multiple viral agents in a single assay. This multiplex system will allow for high throughput screening at reduced cost and will be used in support of the SPF colony development.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Resource-Related Research Projects--Cooperative Agreements (U24)
Project #
5U24RR018144-03
Application #
6791350
Study Section
National Center for Research Resources Initial Review Group (RIRG)
Program Officer
Harding, John D
Project Start
2002-09-30
Project End
2007-08-31
Budget Start
2004-09-01
Budget End
2005-08-31
Support Year
3
Fiscal Year
2004
Total Cost
$1,363,163
Indirect Cost
Name
University of California Davis
Department
Veterinary Sciences
Type
Other Domestic Higher Education
DUNS #
047120084
City
Davis
State
CA
Country
United States
Zip Code
95618
Day, George Q; Ng, Jillian; Oldt, Robert F et al. (2018) DNA-based Determination of Ancestry in Cynomolgus Macaques (Macaca fascicularis). J Am Assoc Lab Anim Sci 57:432-442
Kanthaswamy, Sree; Ng, Jillian; Broatch, Jennifer et al. (2016) Mitigating Chinese-Indian rhesus macaque (Macaca mulatta) hybridity at the California National Primate Research Center (CNPRC). J Med Primatol 45:333-335
Ng, Jillian; Trask, Jessica Satkoski; Smith, David Glenn et al. (2015) Heterospecific SNP diversity in humans and rhesus macaque (Macaca mulatta). J Med Primatol 44:194-201
Oxford, Kristie L; Dela Pena-Ponce, Myra Grace A; Jensen, Kara et al. (2015) The interplay between immune maturation, age, chronic viral infection and environment. Immun Ageing 12:3
Ng, Jillian; Trask, Jessica Satkoski; Houghton, Paul et al. (2015) Use of genome-wide heterospecific single-nucleotide polymorphisms to estimate linkage disequilibrium in rhesus and cynomolgus macaques. Comp Med 65:62-9
Ng, Jillian; Fass, Joseph N; Durbin-Johnson, Blythe et al. (2015) Identifying rhesus macaque gene orthologs using heterospecific human CNV probes. Genom Data 6:202-7
Kanthaswamy, Sree; Ng, Jillian; Ross, Cody T et al. (2013) Identifying human-rhesus macaque gene orthologs using heterospecific SNP probes. Genomics 101:30-7
Satkoski Trask, Jessica A; Garnica, Wendy T; Smith, David Glenn et al. (2013) Single-nucleotide polymorphisms reveal patterns of allele sharing across the species boundary between rhesus (Macaca mulatta) and cynomolgus (M. fascicularis) macaques. Am J Primatol 75:135-44
Kanthaswamy, Sreetharan; Trask, Jessica Satkoski; Ross, Cody T et al. (2012) A large-scale SNP-based genomic admixture analysis of the captive rhesus macaque colony at the California National Primate Research Center. Am J Primatol 74:747-57
Johnson, Z P; Eady, R D; Ahmad, S F et al. (2012) Immunogenetic Management Software: a new tool for visualization and analysis of complex immunogenetic datasets. Immunogenetics 64:329-36

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