title: Further mapping of the Idd5.1 locus for autoimmune diabetes in NOD mice.
abstract: The Idd5 locus for autoimmune diabetes in nonobese diabetic (NOD) mice has been mapped to the proximal half of chromosome 1 and appears to include two loci, Idd5.1 and Idd5.2, Idd5.1 being a candidate homolog of the human IDDM12 locus. Using new recombinant congenic lines, we have reduced the Idd5.1 interval to 5 cM at most, between D1Mit279 and D1Mit19 (not included). This interval now excludes the Casp8 and Cflar (Flip) candidate genes. It still retains Cd28 and Ctla4 and also includes Icos (inducible costimulator). The previously reported differential expression of Ctla4, which is induced at a lower level in NOD than in B6-activated T-cells, was found independent of Idd5.1 itself because Ctla4 expression was induced at a low level in T-cells from Idd5.1-congenic mice. The Idd5.1 locus protected against both spontaneous and cyclophosphamide-induced diabetes, but it did not prevent inflammatory infiltration of the islets of Langerhans. Furthermore, diabetogenic precursor spleen cells from prediabetic NOD and Idd5.1-congenic mice were equally capable of transferring diabetes to immunodeficient NOD.scid/scid recipient mice. The Idd5.1 locus might affect a late event of disease development, subsequent to the onset of insulitis and possibly taking place in the islets of Langerhans.
authors.affiliation: Institut National de Santé et de Recherche Médicale (INSERM) U25, Hôpital Necker-Enfants malades, Paris, France.
authors.forename: S E
authors.initials: SE
authors.lastname: Lamhamedi-Cherradi
authors.forename: O
authors.initials: O
authors.lastname: Boulard
authors.forename: C
authors.initials: C
authors.lastname: Gonzalez
authors.forename: N
authors.initials: N
authors.lastname: Kassis
authors.forename: D
authors.initials: D
authors.lastname: Damotte
authors.forename: L
authors.initials: L
authors.lastname: Eloy
authors.forename: G
authors.initials: G
authors.lastname: Fluteau
authors.forename: M
authors.initials: M
authors.lastname: Lévi-Strauss
authors.forename: H J
authors.initials: HJ
authors.lastname: Garchon
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000235:genetics*; D002874:Chromosome Mapping; D003520:Cyclophosphamide; D003922:Diabetes Mellitus, Type 1 / Q000139:chemically induced / Q000235:genetics* / Q000276:immunology; D020022:Genetic Predisposition to Disease; D007166:Immunosuppressive Agents; D051379:Mice; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD / Q000235:genetics*; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length
chemical_list: D007166:Immunosuppressive Agents; D003520:Cyclophosphamide