O'Shea H, Yousaf N, Altmann D, Fehervari Z, Tonks P, Hetherington C, Harach S, Bland C, Cooke A, Lund T
Division of Immunology, Department of Pathology, University of Cambridge, Cambridge, UK.
Scand J Immunol. 2006 Jan;63(1):17-25. doi: 10.1111/j.1365-3083.2006.001701.x.
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.
非肥胖糖尿病（NOD）小鼠1型糖尿病的发生受主要组织相容性复合体（MHC）II类基因影响。由于导入Ead基因而表达H2-E的NOD-E转基因小鼠可免受1型糖尿病的侵害。虽然保护机制尚不清楚，但这种效应被视为MHC保护免受自身免疫的模型系统。我们研究了Ea启动子区域缺失的影响，这反过来又会影响转基因NOD小鼠中的H2-E表达模式。我们构建了转基因NOD小鼠，其中Ead基因的X（DeltaX）和Y（DeltaY）框分别被功能性缺失。以前使用通过将适当的转基因从C57BL/6转基因小鼠杂交到NOD背景上制备的X或Y框缺失的H2-E转基因小鼠的报告表明，启动子突变消除了在NOD-E中看到的H2-E介导的保护作用。本研究中产生的NOD DeltaX和NOD DeltaY转基因小鼠在糖尿病易感性方面与野生型NOD小鼠不同。NOD DeltaY1动物可免受糖尿病的发展，而DeltaX小鼠仍然易感，尽管程度低于亲本NOD品系。
