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Combination of multiple genes from lupus and diabetes prone mice leads to a novel mouse model for lupus
Author(s) -
Sim Davis Lok,
Bagavant Harini,
Ge Yan,
Gaskin Felicia,
Fu ShuMan,
Deshmukh Umesh S
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.667.12
Subject(s) - lupus nephritis , autoimmunity , systemic lupus erythematosus , nod , immunology , nod mice , serology , autoimmune disease , medicine , anti dsdna antibodies , phenotype , autoantibody , lupus erythematosus , antibody , diabetes mellitus , disease , biology , gene , endocrinology , genetics
The multigenic nature of systemic lupus erythematosus (SLE) is responsible for the varied serological and clinical manifestations observed in patients. Depending on the genotype, spontaneous mouse models of lupus only recapitulate certain features of the disease. This study was undertaken to test the hypothesis, that a mouse with a combination of most autoimmune genes would develop lupus similar to that seen in patients. For this purpose we crossed the lupus‐prone NZM2328 mice with the diabetes‐prone NOD mice and investigated the female F1 mice for autoimmunity. While the female F1 mice did not develop any diabetes, they developed severe proteinuria with >80% incidence by 10 months of age. Kidneys showed glomerular IgG and C3 deposits, with onset of acute proliferative GN between 3–5 months and chronic GN by 7 months of age. All F1 females developed ANA and anti‐dsDNA antibody. Also, sera from 70% of F1 mice immunoprecipitated the snRNP particle compared to only 20% NOD mice and 0% NZM2328 mice. The F1 mice showed elevated expression of type 1 interferon (IFN) inducible genes, in comparison to the NOD mice. Our study demonstrates that combination of multiple autoimmune genes from the NZM2328 and NOD mice results in a novel spontaneous mouse model for lupus nephritis. The disease phenotype in this model represents a large fraction of the human SLE patients.