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ABSTRACT INSULIN-dependent diabetes mellitus (IDDM) is a disease with an autoimmune aetiology. The inbred non-obese diabetic (NOD) mouse strain provides a good animal model of the human
disease1 and genetic analysis suggests that, as in man, at least one of the several genes controlling the development of IDDM is linked to the major histocompatibility complex2,3. The NOD
mouse does not express I-E2 owing to a deletion in the promoter region of the I-E α-chain gene, and the sequence of NOD I-A β-chain in the first external domain is unique with His 56 and Ser
57 (ref. 4) replacing Pro and Asp, respectively, at these positions. There has been considerable interest in the role amino acid 57 might have in conferring susceptibility to autoimmune
diseases, including IDDM. The presence of a charged residue (such as Asp) at this position might affect the conformation of the peptide binding groove5. But it could be assumed that Pro 56
gives rise to a different conformation of I-A β-chain than does His 56. We therefore constructed transgenic NOD mice in which the transgene encoded a modified Aβnod with Pro 56, and studied
its effect on the development of IDDM in this mouse strain. Previous studies have suggested that NOD mice expressing I-E as a result of the introduction of an I-E α-chain (Eα) transgene are
potected from the development of insulitis and hence IDDM6,7. To explore further the protective effect of this molecule we constructed a second class of transgenic NOD mouse carrying an Eαd
transgene. Both transgenes protected the mice from IDDM, but this was not associated with a complete deletion of any T cells expressing commonly used T-cell receptor V β genes. Access
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SIMILAR CONTENT BEING VIEWED BY OTHERS I-AG7 Β56/57 POLYMORPHISMS REGULATE NON-COGNATE NEGATIVE SELECTION TO CD4+ T CELL ORCHESTRATORS OF TYPE 1 DIABETES Article 20 February 2023
SYNGENEICALLY TRANSPLANTED INSULIN PRODUCING CELLS DIFFERENTIATED FROM ADIPOSE DERIVED STEM CELLS UNDERGO DELAYED DAMAGE BY AUTOIMMUNE RESPONSES IN NOD MICE Article Open access 07 April 2022
ISLET CELL REPLACEMENT AND TRANSPLANTATION IMMUNOLOGY IN A MOUSE STRAIN WITH INDUCIBLE DIABETES Article Open access 31 May 2022 REFERENCES * Makino, S. K. _et al._ _Exp. Anim._ 29, 1–13
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_Analyt. Biochem._ 162, 156–159 (1987). Article CAS Google Scholar Download references AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * University College and Middlesex School of Medicine,
40-50 Tottenham Street, London, WIP 9PG, UK Torben Lund, Lorraine O'Reilly, Patricia Hutchings, Robert Gravely & Anne Cooke * Department of Pathology, Washington University, School
of Medicine, 660 South Euclid Avenue, St Louis, Missouri, USA Osami Kanagawa * Clinical Research Centre, Watford Road, Harrow, Middlesex, HA1 3UJ, UK Elizabeth Simpson, Phillip Chandler,
Julian Dyson, Jean K. Picard & Andrew Edwards * National Institute for Medical Research, The Ridgeway, Mill Hill, NW7 1AA, UK Dimitris Kioussis Authors * Torben Lund View author
publications You can also search for this author inPubMed Google Scholar * Lorraine O'Reilly View author publications You can also search for this author inPubMed Google Scholar *
Patricia Hutchings View author publications You can also search for this author inPubMed Google Scholar * Osami Kanagawa View author publications You can also search for this author inPubMed
Google Scholar * Elizabeth Simpson View author publications You can also search for this author inPubMed Google Scholar * Robert Gravely View author publications You can also search for
this author inPubMed Google Scholar * Phillip Chandler View author publications You can also search for this author inPubMed Google Scholar * Julian Dyson View author publications You can
also search for this author inPubMed Google Scholar * Jean K. Picard View author publications You can also search for this author inPubMed Google Scholar * Andrew Edwards View author
publications You can also search for this author inPubMed Google Scholar * Dimitris Kioussis View author publications You can also search for this author inPubMed Google Scholar * Anne Cooke
View author publications You can also search for this author inPubMed Google Scholar RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Lund, T.,
O'Reilly, L., Hutchings, P. _et al._ Prevention of insulin-dependent diabetes mellitus in non-obese diabetic mice by transgenes encoding modified I-A β-chain or normal I-E α-chain.
_Nature_ 345, 727–729 (1990). https://doi.org/10.1038/345727a0 Download citation * Received: 25 April 1990 * Accepted: 14 May 1990 * Issue Date: 21 June 1990 * DOI:
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