The overall significance of this project is that: 1) it will contribute to fulfilling he national need for Indian-origin specific pathogen free (SPF) rhesus monkeys (Macaca mulatta) for AIDS-related research using state of the art viral testing methods; 2) it will provide pedigree monkeys with known genetic relationships from two genetically diverse colonies, and 3) it will provide monkeys that are characterized for MHC Class I alleles, as well as for >50,000 SNPs. The Southwest National Primate Research Center (SNPRC) is in a unique position to provide genetically characterized, SPF, Indian-origin rhesus macaques to the national AIDS-related research effort. The SNPRC houses two genetically and physically separate SPF rhesus macaque colonies. Colony 1 represents the original SNPRC colony supported through the previous efforts of this program (under SNPRC management since 2000), while Colony 2 is a new colony to this program initiated with animals derived from the well-characterized SPF colony from New England NPRC (SPF colony initiated in 1988).
The specific aims are as follows: 1. To make approximately 75 SPF rhesus macaques available for research annually from Colony 1 (current census 474) and to produce offspring from Colony 2 (current census 260) for expansion of the colony and provision of 55 animals for research beginning in the fourth year of the grant, Year 17. We will maximize the long term efficiency of colony production by genetically and reproductively managing both colonies. 2. To verify and maintain the SPF status of the colonies by screening for herpes B virus, SIV, SRV, and STLV-1. The initial viral screening will be performed by serology for all four viruses using the Luminex technology with beads containing two antigens for each virus, and by PCR for SRV. Confirmatory screening by western blot and PCR will be outsourced to California NPRC and the National B Virus Resource Center. 3. To maximize the value of the animals for AIDS-related research purposes by characterizing them for MHC Class I alleles. All progeny will be typed for MHC Class I haplotypes using deep sequencing at the Wisconsin NPRC. The MHC Class I data will be used to maintain diversity in haplotypes, while ensuring appropriate frequencies of specific alleles for AIDS research. High throughput sequencing will provide the genetic markers to ensure Indian-origin and pedigree, but also will increase our capacity for genetic management of the colony and the ability to provide animals with greater genetic characterization to investigators. An SPF Oversight Committee, formed by the two PIs and Core Leaders, will review viral testing and genetic data and recommend breeding strategies. Fulfillment of these aims will contribute to ensuring that the supply of Indian-origin, SPF, rhesus monkeys is sufficient to meet the need of the national AIDS research programs.
Indian-origin rhesus macaque monkeys that are not infected with certain natural pathogens (i.e., specific pathogen free, SPF) are the best animal model for developing improved therapies and vaccines against the worldwide AIDS epidemic. There is a national shortage of these monkeys for biomedical research, and that shortage contributes to delays in initiating AIDS-related research projects. The goals of this program are to produce Indian-origin SPF rhesus monkeys that are genetically characterized and to make them available for AIDS-related research.
