Aly/aly mice: A unique model of biliary disease

Koichi Tsuneyama, Naoko Kono, Masahiro Hoso, Hiroyuki Sugahara, Kazuharu Yoshida, Kazuyosh Katayanagi, M. Eric Gershwin, Katsuhiko Saito, Yasuni Nakanuma

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

An autosomal recessive murine mutation, coined 'aly/aly' or 'alymphoplasia,' was recently reported. Homozygotes for aly are defective in both humoral and cell-mediated immune function and have diffuse lymphoid cell infiltration of various tissues, particularly around the conduit ducts of the pancreas and salivary glands. In pilot studies in our laboratories, aly/aly mice were found to have peculiar biliary tract lesions, which were analyzed histologically and immunohistochemically in the present study. The livers of aly/aly mice older than 8 weeks consistently showed a variable lymphoid cell infiltration with lymph follicle formation in portal tracts; intrahepatic biliary epithelial cells showed various types of damage including pseudopyloric gland metaplasia and proliferative changes. In addition, the extrahepatic bile duct and intrahepatic large bile duct were found to contain an acidophilic substance in their epithelial cytoplasm. In the lumen and occasionally in the cytoplasm of these bile ducts, acidophilic crystals were also seen. Ultrastructurally, the intracytoplasmic acidophilic substances consisted of membrane-bound intracytoplasmic inclusions with homogeneous electron density, likely derived from rough endoplasmic reticulum (ER). Immunohistochemically, the cytoplasmic acidophilic substances were simultaneously positive for cystatin C, gastrin, serotonin, and somatostatin. In contrast, the acidophilic crystals did not react with any of these antibodies. These findings suggest that the intracytoplasmic acidophilic substances may contain a precursor of the peptide hormones, possibly because of defective secretion or intracellular transport. We believe that the aly/aly mouse is a useful model for the analysis of biliary metabolic events, and for studies of the interaction of the immune system and biliary destruction.

Original languageEnglish (US)
Pages (from-to)1499-1507
Number of pages9
JournalHepatology
Volume27
Issue number6
DOIs
StatePublished - 1998

Fingerprint

Cytoplasm
Lymphocytes
Intrahepatic Bile Ducts
Extrahepatic Bile Ducts
Cystatin C
Peptide Hormones
Rough Endoplasmic Reticulum
Gastrins
Metaplasia
Homozygote
Biliary Tract
Lymph
Bile Ducts
Somatostatin
Salivary Glands
Pancreas
Immune System
Serotonin
Epithelial Cells
Electrons

ASJC Scopus subject areas

  • Hepatology

Cite this

Tsuneyama, K., Kono, N., Hoso, M., Sugahara, H., Yoshida, K., Katayanagi, K., ... Nakanuma, Y. (1998). Aly/aly mice: A unique model of biliary disease. Hepatology, 27(6), 1499-1507. https://doi.org/10.1002/hep.510270606

Aly/aly mice : A unique model of biliary disease. / Tsuneyama, Koichi; Kono, Naoko; Hoso, Masahiro; Sugahara, Hiroyuki; Yoshida, Kazuharu; Katayanagi, Kazuyosh; Gershwin, M. Eric; Saito, Katsuhiko; Nakanuma, Yasuni.

In: Hepatology, Vol. 27, No. 6, 1998, p. 1499-1507.

Research output: Contribution to journalArticle

Tsuneyama, K, Kono, N, Hoso, M, Sugahara, H, Yoshida, K, Katayanagi, K, Gershwin, ME, Saito, K & Nakanuma, Y 1998, 'Aly/aly mice: A unique model of biliary disease', Hepatology, vol. 27, no. 6, pp. 1499-1507. https://doi.org/10.1002/hep.510270606
Tsuneyama K, Kono N, Hoso M, Sugahara H, Yoshida K, Katayanagi K et al. Aly/aly mice: A unique model of biliary disease. Hepatology. 1998;27(6):1499-1507. https://doi.org/10.1002/hep.510270606
Tsuneyama, Koichi ; Kono, Naoko ; Hoso, Masahiro ; Sugahara, Hiroyuki ; Yoshida, Kazuharu ; Katayanagi, Kazuyosh ; Gershwin, M. Eric ; Saito, Katsuhiko ; Nakanuma, Yasuni. / Aly/aly mice : A unique model of biliary disease. In: Hepatology. 1998 ; Vol. 27, No. 6. pp. 1499-1507.
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