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. 1979 Oct;76(10):5289–5293. doi: 10.1073/pnas.76.10.5289

Autoimmune and lymphoproliferative disease in (B6-GIX+ × 129) F1 mice: Relation to naturally occurring antibodies against murine leukemia virus-related cell surface antigens

Yuichi Obata 1, Toshio Tanaka 1,*, Elisabeth Stockert 1, Robert A Good 1
PMCID: PMC413127  PMID: 228283

Abstract

GIX congeneic mouse strains, C57BL/6-GIX+(B6-GIX+) and 129-GIX-, have been derived from the prototype strains, B6(GIX-) and 129(GIX+). The hybrids, (B6-GIX+ × 129)F1 (GIX+F1) and (B6 × 129-GIX-)F1 (GIX-F1), differ only in regard to genetic loci controlling GIX antigen expression. GIX+F1 mice spontaneously produce GIX antibody and often show signs of autoimmune disease and lymphoproliferative disease. GIX-F1 mice and mice of the two parental strains (B6-GIX+ and 129) of GIX+F1 do not produce GIX antibody and seldom show signs of these diseases. G(ERLD), and G(RADA1), antibodies, natural thymocytotoxic autoantibody, and antinuclear antibodies were produced by GIX+F1 mice. However, these four antibodies were also found in the other strains. GIX+F1 mice develop pronounced diffuse glomerulonephritis similar to that found in systemic lupus erythematosus in man. Incidence studies in which mice were examined according to age rather than state of health showed that the lesions occurred in 38% of GIX+F1 mice but not in GIX-F1, B6-GIX+, or 129 mice. Lymphoproliferative lesions were either reticulum cell sarcoma (RCS) type A or reactive lymphoid hyperplasia (RLH). RCS occurred more often in GIX+F1 (38%) than in GIX-F1 (12%) or B6-GIX+ (8%). No RCS occurred in mice of the 129 strain. RLH occurred in GIX+F1 mice (10%) but not in the other strains. From these results, the following conclusions are drawn: (i) Severe glomerulonephritis and the increased occurrence of lymphoproliferative lesions in these animals depend on the presence of GIX antigen; (ii) besides genes controlling GIX antigen expression, other genes from both parental strains are required to create the basis in the progeny F1 mice for the development of these diseases; and (iii) the chronic production of GIX antibody may be necessary for the development of the severe glomerulonephritis and for the increased occurrence of lymphoproliferative diseases in GIX+F1 mice.

Keywords: congeneic mouse strains, GIX antibody production, systemic lupus erythematosus-type nephritis, reticulum cell sarcoma

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

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