Pathogenomics of a multifactorial disease : Lessons from an MRL/Ipr mouse model :

NDLデジタルコレクション
  • Nose,M
    Department of Pathology, Ehime University School of Medicine
  • Terada,M
    Department of Pathology, Ehime University School of Medicine
  • Nishihara,M
    Department of Pathology, Ehime University School of Medicine
  • Kamogawa,J
    Department of Pathology, Ehime University School of Medicine
  • Miyazaki,T
    Department of Pathology, Ehime University School of Medicine
  • Qu,WM
    Department of Pathology, Ehime University School of Medicine
  • Lu,LM
    Department of Pathology, Ehime University School of Medicine
  • Yamada,A
    Department of Pathology, Ehime University School of Medicine
  • Ito,MR
    Department of Pathology, Ehime University School of Medicine
  • Ono,M
    Department of Pathology, Ehime University School of Medicine
  • Mori,S
    Department of Oral and Maxillofacial Surgery, Tohoku University School of Dentistry
  • Nakatsuru,S
    KAN Research Institute

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Recent advances in genomics of human and mouse can be expected to clarify the genetic inheritance of multifactorial diseases and to identify their susceptibility genes by using murine models. Collagen disease has been considered to be a representative ono of multifactorial diseases, which is a syndrome of three overlapping disease categories; connective tissue disease, rheumatic disease and autoimmune diseasc, involving systemic lupus erythematosus, rheumatoid arthritis, polyarteritis nodosa, Sjogren's syndrome, etc. However, their pathological findings show complex lesions such as glomerulonephritis, vasculitis, arthritis, and/or sialoadenitis, etc. Thus, it is still controversial whether such diversity and similarity of pathological manifestations among the collagen disease depends on ambiguity in diagnosis or is an intrinsic quality of the diseases themselves. An MRL/Mp-lpr/lpr (MRL/lpr) strain of mice shows various forms of collagen disease, including glomerulonephritis, vasculitis, polyarthritis and sialoadenitis. On a series of our genetic studies with total genome analyses of MRL/lpr mice, we identified the susceptibility loci to each lesions to point out the significance of polygenic inheritance in collagen disease. Then, it allows us to conclude that the diversity and similarity of the pathological manifestations among various disease categories in collagen disease will be a result of the combination of polygenes. These genes, including both susceptible and resistant ones, may regulate cascade reactions leading to the pathological manifestations via the expression of functional proteins which differ quantitatively and/or qualitatively based on allelic polymorphism. Further identifying human candidate genes may improve the diagnostic criteria and categorization of collagen diseases should provide promising clues for determining the prognosis of patients with collagen disease.

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