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Effect of X‐ and Y‐Box Deletions on the Development of Diabetes in H‐2Eα‐Chain Transgenic Nonobese Diabetic Mice
Author(s) -
O'Shea H.,
Yousaf N.,
Altmann D.,
Fehervari Z.,
Tonks P.,
Hetherington C.,
Harach S.,
Bland C.,
Cooke A.,
Lund T.
Publication year - 2006
Publication title -
scandinavian journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.934
H-Index - 88
eISSN - 1365-3083
pISSN - 0300-9475
DOI - 10.1111/j.1365-3083.2006.001701.x
Subject(s) - nod , nod mice , transgene , genetically modified mouse , major histocompatibility complex , biology , mutation , gene , autoimmunity , immunology , genetics , immune system
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 Ea d 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 Ea d 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.