A novel spontaneous mutation in the TAP2 gene unravels its role in macrophage survival

Summary We report a new mouse strain with a single point mutation in the type 2 transporter associated with antigen processing (TAP2). This strain randomly arose in one of our C57BL/6J mouse colonies and was initially discovered because of the lack of CD8 + T cells in the periphery. Following our observation, we subsequently revealed a lack of cell surface MHC‐I expression, derived from TAP2 protein deficiency. Our strain, named eightless , has a C to T substitution in exon 5 resulting in a glutamine to stop codon substitution at position 285 in the TAP2 protein. Interestingly, in addition to the expected lack of CD8 + T cell phenotype, eightless mice have a diminished number of macrophages in their peritoneum. Moreover, following peritoneal inflammation, elicited eightless macrophages showed impaired survival both in vivo and ex vivo . Our study describes the first ever TAP2 complete knockout mouse strain and provides a possible explanation for why patients with TAP2 deficiency syndrome present clinical manifestations that would suggest a phagocyte defect rather than a lack of CD8 + T cells.