Abstract
Abstract The SHrN™ scid hairless NOD mouse was developed to provide a hairless triple-immunodeficient mouse model to the research community. The non-obese diabetic (NOD) mouse carrying the Prkdcscid mutation (NOD scid mouse) is an established xenograft model for humanization, oncology, and immunology research. It has proven to be particularly useful in elucidating mechanisms of spontaneous lymphoma and thymic tumors, prostate cancer research, and the engraftment of hematopoietic stem cells. As scid mice are haired, it is often necessary to shave these mice to facilitate tumor observation and evaluation. However, shaving animals does not prevent autofluorescence of hair follicles while imaging scid mice. We have transferred the hairless mutation (Hrhr) from the outbred HsdOla:MF1-Hrhr to the NOD.CB17-Prkdcscid/NCrHsd mouse to generate the inbred hairless NOD.Cg-Prkdcscid Hrhr/NCrHsd mouse, or commonly named scid hairless NOD (SHrN™). Herein we describe the breeding program utilized to generate the SHrN™ model using marker assisted backcrossing methodology. A combination of single nucleotide polymorphism (SNP) allelic discrimination and quantitative PCR (QPCR) analysis was employed to genotype offspring for the Prkdcscid and Hrhr mutations. SNP genotypes were determined using the Fluidigm Biomark™ High Throughput SNP Genotyping Platform. In each backcross generation, a total of 560 SNPs was measured on all offspring homozygous for Prkdcscid and heterozygous for Hrhr to select the most optimal breeders with the highest percentage of NOD genetic background. Littermates identified to have a genetic background 99% concordant to the NOD mouse were sibling-mated to produce F1 breeders homozygous for both Prkdcscid and Hrhr mutations. The immunologic characteristics of this model are also described, which include B and T cell deficiency, a functional deficit of NK cells, and decreased macrophage and complement function. As the least leaky, most immunocompromised hairless model available, the SHrN™ model will become a valuable enhancement to oncology and immunology research, with particular benefit to imaging technology studies. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 393.
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