title: A novel spontaneous mutation in the TAP2 gene unravels its role in macrophage survival.
abstract: 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.
authors.affiliation: The Lautenberg Centre for Immunology and Cancer Research, The Biomedical Research Institute Israel-Canada of the Faculty of Medicine, The Hebrew University Hadassah Medical School, Jerusalem, Israel.
authors.forename: Antonio
authors.initials: A
authors.lastname: Lapenna
authors.affiliation: The Lautenberg Centre for Immunology and Cancer Research, The Biomedical Research Institute Israel-Canada of the Faculty of Medicine, The Hebrew University Hadassah Medical School, Jerusalem, Israel.
authors.forename: Ibrahim
authors.initials: I
authors.lastname: Omar
authors.affiliation: The Lautenberg Centre for Immunology and Cancer Research, The Biomedical Research Institute Israel-Canada of the Faculty of Medicine, The Hebrew University Hadassah Medical School, Jerusalem, Israel.
authors.forename: Michael
authors.initials: M
authors.lastname: Berger
mesh_terms: D000071450:ATP Binding Cassette Transporter, Subfamily B, Member 3 / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000502:physiology*; D002470:Cell Survival / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D005091:Exons / Q000235:genetics*; D005260:Female; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000235:genetics*; D008264:Macrophages / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009154:Mutation / Q000235:genetics*; D010537:Peritoneum / Q000473:pathology*
chemical_list: D000071450:ATP Binding Cassette Transporter, Subfamily B, Member 3; D015395:Histocompatibility Antigens Class I; C489516:Tap2 protein, mouse
keywords: T cells; immunodeficiency diseases; major histocompatibility complex