linical Development une Competency of a Hairless Mouse Strain for Improved Ther clinical Studies in Genetically Engineered Mice

nloaded etically engineered mouse models (GEMM) of cancer are of increasing value to preclinical therapeutics. l imaging is a cost-effective method of assessing deep-seated tumor growth in GEMMs whose tumors encoded to express luminescent or fluorescent reporters, although reporter signal attenuation would roved if animals were fur-free. In this study, we sought to determine whether hereditable furlessness ng from a hypomorphic mutation in the Hairless gene would or would not also affect immune compeBy assessing humoral and cellular immunity of the SKH1 mouse line bearing the hypomorphic Hairless ion, we determined that blood counts, immunoglobulin levels, and CD4+ and CD8+ T cells were rable between SKH1 and the C57Bl/6 strain. On examination of T-cell subsets, statistically significant nces in naïve T cells (1.7 versus 3.4 × 10 cells/spleen in SKH1 versus C57Bl/6, P = 0.008) and memory (1.4 versus 0.13 × 10 cells/spleen in SKH1 versus C57Bl/6, P = 0.008) were detected. However, merical differences did not result in altered T-cell functional response to antigen rechallenge (keyhole hemocyanin) in a lymph node cell in vitro proliferative assay. Furthermore, interbreeding the SKH1 line to a rhabdomyosarcoma GEMM showed preserved antitumor responses of CD56+ natural killer nd CD163+ macrophages, without any differences in tumor pathology. The fur-free GEMM was also ally amenable to multiplex optical imaging. Thus, SKH1 represents an immune competent, fur-free especi mouse strain that may be of use for interbreeding to other genetically engineered mouse models of cancer for improved preclinical studies. Mol Cancer Ther; 9(8); 2354–64. ©2010 AACR.