Genetic dissection of the complex pathological manifestations of collagen disease in MRL/lpr mice

Syuichi Nakatsuru, Miho Terada, Miyuki Nishihara, Junji Kamogawa, Tatsuhiko Miyazaki, Wei Min Qu, Koji Morimoto, Chie Yazawa, Hideaki Ogasawara, Yoriko Abe, Keiko Fukui, Go Ichien, Mitsuko R. Ito, Shiro Mori, Yusuke Nakamura, Masato Nose

Research output: Contribution to journalArticlepeer-review

25 Citations (Scopus)

Abstract

An MRL strain of mice bearing a Fas-deletion mutant gene, lpr, MRL/MpJ- lpr/lpr (MRL/lpr) develops collagen disease involving vasculitis, glomerulonephritis, arthritis and sialoadenitis, each of which has been studied as a model for polyarteritis, lupus nephritis, rheumatoid arthritis and Sjogren's syndrome, respectively. Development of such lesions seems dependent on host genetic background since the congenic C3H/HeJ-lpr/lpr (C3H/lpr) mice rarely develop them. To identify the gene loci affecting each lesion, a genetic dissection of these complex pathological manifestations was carried out. First, histopathological features in MRL/lpr, C3H/lpr, (MRL/lpr x C3H/lpr) F1 intercross, and MRL/lpr x (MRL/lpr x C3H/lpr) F1 backcross mice were analyzed. Genomic DNA of the backcross mice were subjected to association studies by Chi-squared analysis for determining which polymorphic microsatellite locus occurs at higher frequency among affected compared to unaffected individuals for each lesion. As a result, gene loci recessively associated with each lesion were mapped on different chromosomal positions. We concluded that each of these lesions in MRL/lpr mice is under the control of a different set of genes, suggesting that the complex pathological manifestations of collagen disease result from polygenic inheritance.

Original languageEnglish
Pages (from-to)974-982
Number of pages9
JournalPathology international
Volume49
Issue number11
DOIs
Publication statusPublished - 1999 Dec 1

Keywords

  • Animal model
  • Arthritis
  • Glomerulonephritis
  • Mouse genetics
  • Sialoadenitis
  • Vasculitis

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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