The NOD mouse is widely used as a model of organ-specific autoimmunity because it develops specific autoimmune destruction of pancreatic β-cells. Although it is clear that T-cells and monocytes are necessary for β-cell destruction, humoral factors, such as antibodies and complement, may also contribute to tissue damage. Attempts to cure diabetes in experimental models by immunoisolation of transplanted islets has raised the need to protect the islets from the relatively small components of the complement cascade. In this study, we report that NOD mice have no complement lytic activity and that the exclusion of complement is unnecessary in this model. Sera from young NOD mice were unable to lyse sheep red blood cells coated with rabbit antibody. Lytic activity of NOD sera was reconstituted by mixing with C4-deficient CBA sera, but not C5-deficient DBA/2 sera, indicating the presence of C4, but the absence of C5 activity in NOD sera. Lytic activity of NOD sera could be reconstituted with human C5 electrofocused in polyacrylamide gel. The polymerase chain reaction was used to amplify fragments from genomic DNA corresponding to the region of Hc (the gene encoding C5) in DBA/2 mice, which carries a 2–base pair deletion responsible for the lack of C5 protein expression in these mice. DBA/2 and NOD mice from several colonies produced a fragment 2 bases shorter than that generated from the wild-type allele in BALB/c mice. We concluded that NOD mice have no complement lytic activity as they lack C5 because of a 2–base pair deletion in the coding region of He and that the NOD mouse is not an appropriate model to test the need for complement exclusion from immunoisolation chambers in the treatment of diabetes mellitus.
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Original Articles| November 01 1993
Complement Lytic Activity Has No Role in the Pathogenesis of Autoimmune Diabetes in NOD Mice
Alan Geogrge Baxter;
Address correspondence and reprint requests to Dr. Anne Cooke, Cambridge University Department of Pathology, Division of Immunology, Tennis Court Road, Cambridge CB2 1QP, UK.
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Alan Geogrge Baxter, Anne Cooke; Complement Lytic Activity Has No Role in the Pathogenesis of Autoimmune Diabetes in NOD Mice. Diabetes 1 November 1993; 42 (11): 1574–1578. https://doi.org/10.2337/diab.42.11.1574
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