Genetic control of inflammatory arthritis and glomerulonephritis in congenic lpr mice and their F1 hybrids

Gary S. Gilkeson, Phillip Ruiz, A. Jane Pritchard, David S. Pisetsky

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

MRL- lpr lpr mice spontaneously develop a complex immunological disease characterized by glomerulonephritis, inflammatory erosive arthritis and the production of rheumatoid factors (RF) and anti-DNA antibodies. We have previously reported that, of congenic lpr strains, only MRL- lpr lpr mice develop synovial pathology suggesting that both the lpr gene and another gene(s) in the MRL background are necessary for the development of arthritis. To define further the genetics of arthritis and its relationship to glomerulonephritis and autoantibody production, we studied disease expression in MRL- lpr lpr and C57BL 6- lpr lpr mice and their offspring (BM- lpr lpr and MB- lpr lpr). At 6 months of age these mice were killed and bled, and their kidneys and knee joints were removed for pathological studies. Fourteen of 28 MB- lpr lpr mice displayed synovial hypertrophy, while eight of 28 had significant synovial inflammation. BM- lpr lpr mice showed similar changes: nine of 22 and eight of 22 exhibited synovial hypertrophy and inflammation respectively. Joints from MRL- lpr lpr mice revealed 13 of 17 with synovial hypertrophy and 12 of 17 with inflammation, while none of 14 B6- lpr lpr mice had synovial changes. Renal pathology was minimal in the F1 mice with only mild hypercellularity in seven of 21 MB- lpr lpr and five of 22 BM- lpr lpr mice. All MRL- lpr lpr mice, in contrast, had marked glomerular changes with 12 of 17 exhibiting glomerular crescents. Only one F1 mouse had both arthritis and renal abnormalities. IgM RF levels were elevated in all four experimental groups, but did not correlate with the presence or severity of arthritis. IgG RF levels were elevated in the MB- lpr lpr and MRL- lpr lpr mice, but did not correlate with the degree of arthritis. These results indicate that renal disease and arthritis develop independently in lpr mice, possibly on a genetic basis, and that the presence and titer of autoantibodies do not correlate with tissue injury.

Original languageEnglish (US)
Pages (from-to)595-606
Number of pages12
JournalJournal of Autoimmunity
Volume4
Issue number4
DOIs
StatePublished - Aug 1991

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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