Effect of X- and Y-box deletions on the development of diabetes in H-2Eα-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 (ΔX) and Y (ΔY) 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 ΔX and NOD ΔY transgenic mice generated in the present study differ in susceptibility to diabetes from wild-type NOD mice. NOD ΔY1 animals are protected from diabetes development, while ΔX mice remain susceptible, albeit to a lesser extent than the parental NOD strain. © 2006 Blackwell Publishing Ltd.