Spontaneous occurrence of chronic non-suppurative destructive cholangitis and antimitochondrial autoantibodies in MRL/lpr mice: Possible animal model for primary biliary cirrhosis

Koichi Tsuneyama, Masato Nose, Miyuki Nisihara, Kazuyoshi Katayanagi, Kenichi Harada, Yasuni Nakanuma

Research output: Contribution to journalArticlepeer-review

20 Citations (Scopus)

Abstract

MRL/MP mice bearing the lymphoproliferative gene lpr (known as MRL/MP-lpr/lpr or MRL/lpr mice) are known to spontaneously develop severe autoimmune diseases such as glomerulonephritis, arteritis and arthritis at an early stage of their life. They have also been reported to develop severe sialadenitis, suggesting that this mouse could be a model for Sjögren's syndrome. Primary biliary cirrhosis, an autoimmune disease characterized by chronic non-suppurative destructive cholangitis and the occurrence of antimitochondrial antibodies, is frequently associated with Sjögren's syndrome. In this study, we examined whether cholangitis and/or antimitochondrial antibodies occur in this mouse model, using more than 100 young and old MRL/lpr mice. We frequently found portal inflammation associated with cholangitis of small intrahepatic bile ducts, especially in older mice. There was also infiltration of inflammatory cells (monocytes) as well as CD4-positive T cells. Epithelioid granuloma and bile-duct loss were also occasionally found. These histological features resemble primary biliary cirrhosis. In addition, antimitochondrial antibodies were shown by immunocytochemistry to be present in the sera of MRL/lpr mice. There is currently no established animal model for primary biliary cirrhosis. Therefore, further studies on MRL/lpr mice, with respect to pathogenesis of primary biliary cirrhosis, are warranted.

Original languageEnglish
Pages (from-to)418-424
Number of pages7
JournalPathology international
Volume51
Issue number6
DOIs
Publication statusPublished - 2001
Externally publishedYes

Keywords

  • Antimitochondrial antibodies
  • Chronic non-suppurative destructive cholangitis
  • MRL/lpr mice
  • Primary biliary cirrhosis
  • Sjögren's syndrome

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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