Genome analysis of collagen disease in MRL/lpr mice: Polygenic inheritance resulting in the complex pathological manifestations

Masato Nose, Miho Terada, Miyuki Nishihara, Junji Kamogawa, Tatsuhiko Miyazaki, Wei Min Qu, Shiro Mori, Syuichi Nakatsuru

Research output: Contribution to journalArticlepeer-review

17 Citations (Scopus)

Abstract

MRL/MpJ-lpr/lpr (MRL/lpr) mice develop 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. In the previous studies, we observed genetic segregation of these complex pathological manifestations throughout the genome recombination with a C57Bl/6-lpr/lpr or a C3H/HeJ-lpr/lpr (C3H/lpr) strain of mice which rarely develops such lesions, indicating that development of collagen disease is dependent on an MRL host genetic background. To clarify the mode of inheritance and the gene loci affecting four types of the lesions in MRL/lpr mice; vasculitis, glomerulonephritis, arthritis and sialoadenitis, a genetic dissection of the lesions was carried out by using MRL/lpr, C3H/lpr, (MRL/lpr x C3H/lpr) F1 intercross, and MRL/lpr x (MRL/lpr x C3H/lpr) F1 backcross mice. Definition of each lesion was performed by histopathology under light microscopy, and genomic DNA of the backcross mice were subjected to association studies by chi-square analysis for determining which polymorphic microsatellite locus occurs at higher frequency among affected compared to unaffected individuals for each lesion. We observed that gene loci recessively associated with each lesion were mapped on different chromosomal positions. We conclude that each of four types of the lesions in MRL/lpr mice is under the control of different set of genes, suggesting the complex pathological manifestations of collagen disease result from polygenic inheritance. (C) 2000 Elsevier Science Ireland Ltd.

Original languageEnglish
Pages (from-to)S53-S61+S63
JournalInternational Journal of Cardiology
Volume75
Issue numberSUPPL. 1
DOIs
Publication statusPublished - 2000 Aug 31

Keywords

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

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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