The goal of this proposal is to expand the production of genetically characterized rhesus macaques of Chinese-ancestry that are specific pathogen-free (SPF) for 7 persistent viruses, including simian immunodeficiency virus (SIV), simian type D retrovirus (SRV), simian T-lymphotropic virus (STLV), Cercopithecine herpes virus 1 (B virus), simian foamy virus (SFV), rhesus cytomegalovirus (RhCMV) and rhesus rhadinovirus (RRV). This proposed expansion will be geared to the production of SPF animals for use in AIDS-related research, and to establishing a long-term SPF breeding colony of Chinese-origin rhesus macaques with known pedigrees and well-defined MHC genotypes. To meet these objectives, we will continue to derive SPF offspring from conventional, non-SPF Chinese rhesus breeding stock through nursery.-rearing of neonates. In addition, we will expand the existing Chinese-origin SPF colony through natural breeding and mother-rearing in social groups. An expanded program of MHC typing that includes additional microsatellite loci, class I alleles, and class II genes will be used to characterize offspring and their parents. This expanded MHC typing will allow the identification and definition of immune response genotypes, and will allow for selected breeding to produce animals with specific genetic profiles to respond to research needs. We also propose to collect longitudinal data on age-related changes in phenotype and function of lymphocyte subsets in cohorts of nursery-reared and mother-reared SPF rhesus macaques and in cohorts of SPF infants and non-SPF infants with differential exposure to infectious disease agents. Age specific reference ranges, developed from normal, healthy SPF-rhesus macaques, are essential to more fully understand and utilize the macaque model system, and to provide comparative data allowing for more accurate interpretation of lymphocyte subset phenotype and functional alterations observed in AIDS and other infectious and immunologic diseases. Information on the genetics of immunity in SPF macaques will also impact the use of this valuable NHP for research on transplantation and stem cell/regenerative medicine. The scope of work proposed in this application will produce well characterized NHP animal resources for use in NIH-funded AIDS-related research. Genetic and immunologic data obtained from this project will better define and characterize the rhesus macaque model system in support of research on AIDS and other infectious diseases.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Resource-Related Research Projects--Cooperative Agreements (U24)
Project #
5U24RR018144-09
Application #
8080446
Study Section
National Center for Research Resources Initial Review Group (RIRG)
Program Officer
Contreras, Miguel A
Project Start
2002-09-30
Project End
2014-05-31
Budget Start
2011-06-01
Budget End
2014-05-31
Support Year
9
Fiscal Year
2011
Total Cost
$1,256,582
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
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
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; 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
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
Taormina, Patrick L; Satkoski Trask, Jessica A; Smith, David G et al. (2012) Variation in CCL3L1 copy number in rhesus macaques (Macaca mulatta). Comp Med 62:218-24

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