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. 1996 Dec;149(6):1919–1930.

Oval cell proliferation associated with the murine insertional mutation TgN737Rpw.

W G Richards 1, B K Yoder 1, R J Isfort 1, P G Detilleux 1, C Foster 1, N Neilsen 1, R P Woychik 1, J E Wilkinson 1
PMCID: PMC1865369  PMID: 8952527

Abstract

The Tg737 gene was identified by its direct association with a transgene-induced insertion mutation in the mouse. This mutation causes pleiotropic phenotypes including a syndrome similar to autosomal recessive polycystic kidney disease in humans. This syndrome, in addition to renal cyst formation, includes the presence of an invariably associated liver abnormality. The liver pathology in TgN737Rpw mice is characterized by a biliary hyperplasia that includes the proliferation of cells that morphologically and immunologically resemble oval cells, a liver progenitor cell. This abnormality is first observed at approximately 5 days of age in the portal region and then progresses into the periportal regions. Additionally, the formation and proliferation of dysplastic ductular structures are observed from the onset of the phenotype. Serum chemistry indicated that the primary defect is likely to be of biliary origin, and hepatic function appears normal in the mutant mice. Therefore, this mutation is unlike other causes of oval cell proliferation in that the hepatic parenchyma is relatively unaffected. The identification of the Tg737 gene associated with this mutation suggests that it functions in regulating the proliferation/differentiation of oval cells within the liver, which further indicates that this gene may function in pathological conditions that include oval cell proliferation, such as hepatocellular carcinogenesis.

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