title: Effect of X- and Y-box deletions on the development of diabetes in H-2Ealpha-chain transgenic nonobese diabetic mice.
abstract: The development of type 1 diabetes in nonobese diabetic (NOD) mice is influenced by major histocompatibility complex (MHC) class II genes. The NOD-E transgenic mouse, which expresses H2-E as a result of the introduction of an Ead gene, is protected from development of type 1 diabetes. While the mechanism of protection remains unclear, the effect has been regarded as a model system for MHC protection from autoimmunity. We have investigated the effect of deletions of the Ea promoter region, which, in turn, affect H2-E expression patterns in transgenic NOD mice. We have constructed transgenic NOD mice where the X (DeltaX) and Y (DeltaY) boxes of the Ead gene have, respectively, been functionally deleted. Previous reports, using X- or Y-box-deleted H2-E transgenic mice, made by crossing the appropriate transgenes onto the NOD background from C57BL/6 transgenic mice, indicated that promoter mutation abrogated the H2-E-mediated protection seen in NOD-E. The NOD DeltaX and NOD DeltaY transgenic mice generated in the present study differ in susceptibility to diabetes from wild-type NOD mice. NOD DeltaY1 animals are protected from diabetes development, while DeltaX mice remain susceptible, albeit to a lesser extent than the parental NOD strain.
authors.affiliation: Division of Immunology, Department of Pathology, University of Cambridge, Cambridge, UK.
authors.forename: H
authors.initials: H
authors.lastname: O'Shea
authors.forename: N
authors.initials: N
authors.lastname: Yousaf
authors.forename: D
authors.initials: D
authors.lastname: Altmann
authors.forename: Z
authors.initials: Z
authors.lastname: Fehervari
authors.forename: P
authors.initials: P
authors.lastname: Tonks
authors.forename: C
authors.initials: C
authors.lastname: Hetherington
authors.forename: S
authors.initials: S
authors.lastname: Harach
authors.forename: C
authors.initials: C
authors.lastname: Bland
authors.forename: A
authors.initials: A
authors.lastname: Cooke
authors.forename: T
authors.initials: T
authors.lastname: Lund
mesh_terms: D000818:Animals; D003520:Cyclophosphamide / Q000633:toxicity; D003922:Diabetes Mellitus, Type 1 / Q000139:chemically induced / Q000235:genetics* / Q000276:immunology*; D020022:Genetic Predisposition to Disease; D006183:H-2 Antigens / Q000032:analysis / Q000235:genetics*; D007150:Immunohistochemistry; D051379:Mice; D016688:Mice, Inbred NOD; D008822:Mice, Transgenic; D009154:Mutation; D011401:Promoter Regions, Genetic; D017384:Sequence Deletion; D013154:Spleen / Q000276:immunology; D013950:Thymus Gland / Q000276:immunology; D019076:Transgenes / Q000235:genetics
chemical_list: D006183:H-2 Antigens; D003520:Cyclophosphamide