NSG-Hprt^null mice are NOD.scid.Il2Rγc^null ("NSG"; Stock No. 005557) animals also harboring the Hprt^em1Mvw allele (Hprt^null). The Hprt^null mutation has as a frame shift and premature termination, resulting in function knockout. Hprt-deficiency causes hypoxanthine-aminopterin-thymidine (HAT)-inducible cell death, but renders the cell resistant to 6-thioguanine (6-TG) cytotoxicity.

NSG-Hprt^null females homozygous for all three mutations, and males that are homozygous for scid and hemizygous for the X-linked mutations Hprt^null and Il2Rγc^null, may be collectively referred to as homozygous NSG-Hprt^null mice.

These NSG-Hprt^null mice may be expected to have a similar phenotype as the NSG-Hprt^b-m3 model (Stock No. 012480) that has the Hprt^b-m3 knockout rather than the Hprt^em1Mvw knockout. The expected phenotype of NSG-Hprt^null mice is described below.
Although viable and fertile, homozygous NSG-Hprt^null mice are immunodeficient: they have no mature T cells or B cells, lack functional natural killer (NK) cells, have reduced numbers of lymphocytes and myeloid dendritic cells, and are deficient in cytokine signaling. The Hprt-deficiency results in biochemically defective stromal cells.
Like homozygous NSG mice, homozygous NSG-Hprt^null mice are designed to allow engraftment of human tissues and primary cancers, such as hematopoietic cancers (e.g., leukemia), melanoma, ER+ breast cancer xenografts, purified human CD4⁺ T cells (fractionated from human peripheral blood mononuclear cells [PBMC]), and other tissues. When human cancers are implanted in Hprt-deficient NSG mice, the mouse fibroblast and stromal cells replace the human stromal cells. Following tumor explantation into culture, any Hprt-deficient mouse cells can be eliminated by HAT selection; resulting in isolation of human cancer cells. Conversely, Hprt-deficient mouse cells can be enriched by 6-TG selection. These mice may be used to generate patient-specific low passage cell lines from primary cancers for use in chemosensitivity profiling and other applications.

Similar to other immunodeficient strains, maintaining homozygous NSG-Hprt^null mice in high health status (specific pathogen-free) vivaria promotes overall colony health. If homozygous NSG-Hprt^null animals are maintained in low health barrier rooms, the use of medicated water (e.g., sulfatrim/trimethoprim-sulfa or enrofloxacin/Baytril) is suggested to increase overall colony health.

View our Resources for the NSG mouse model, including discussion forum, immunodeficient model comparison, and categorized, up-to-date references.