Analysis of granulomatous arteritis in MRL/Mp autoimmune disease mice bearing lymphoproliferative genes. The use of mouse genetics to dissociate the development of arteritis and glomerulonephritis

M. Nose, M. Nishimura, M. Kyogoku

Research output: Contribution to journalArticle

55 Citations (Scopus)

Abstract

MRL/Mp mice bearing the lymphoproliferation gene (lpr) spontaneously develop systemic granulomatous arteritis coincident with glomerulonephritis (GNP). Although the association of lpr-dependent lymphoproliferation in these mice seems to be a prerequisite for the development of granulomatous arteritis, the genetic basis is poorly understood. The first approach to this problem was to study the ability of another, nonallelic, lymphoproliferative gene, gld (generalized lymphoproliferative disease), inducing arteritis in MRL/Mp mice. The gld gene was placed on an MRL/Mp background by producing reciprocal (MRL/Mp-+/+ x C3H/HeJ-gld/gld)F2 hybrid mice. Seventeen percent of these mice with lymphoproliferation had arteritis and GNP, suggesting that more than one lymphoproliferative gene could induce GNP and arteritis in an MRL/Mp background. Next, the effect of rearrangements in the genetic background of MRL/Mp-lpr/lpr mice by hybridization with non-autoimmune lpr-bearing mice was examined. This was done by making MRL/Mp-lpr/lpr x reciprocal (MRL/Mp-lpr/lpr x C57BL/6-lpr/lpr)F1 mice. Thirty-three percent of these mice developed arteritis, but one third of these did not get GNP, thus showing that susceptibility to arteritis was separate from GNP. The histopathologic features of the arteritis in both the F2 hybrids and the backcross mice were granulomatous and were identical to those seen in MRL/Mp-lpr/lpr mice. These findings suggested that it might be possible to dissociate two components (arteritis and GNP) of a severe autoimmune disease of MRL/Mp mice and to study their pathogenesis separately.

Original languageEnglish
Pages (from-to)271-280
Number of pages10
JournalAmerican Journal of Pathology
Volume135
Issue number2
Publication statusPublished - 1989 Jan 1

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Fingerprint Dive into the research topics of 'Analysis of granulomatous arteritis in MRL/Mp autoimmune disease mice bearing lymphoproliferative genes. The use of mouse genetics to dissociate the development of arteritis and glomerulonephritis'. Together they form a unique fingerprint.

  • Cite this