Biliary dysgenesis in the PCK rat, an orthologous model of autosomal recessive polycystic kidney disease

Tatyana V. Masyuk, Bing Q. Huang, Anatoliy I. Masyuk, Erik L. Ritman, Vicente Torres, Xiaofang Wang, Peter C Harris, Nicholas F La Russo

Research output: Contribution to journalArticle

76 Citations (Scopus)

Abstract

Hepatic polycystic disease occurs alone or in combination with polycystic kidney disease (PKD). In autosomal recessive PKD (ARPKD), liver lesions are the major cause of morbidity and mortality in older patients. ARPKD is caused by a mutation to PKHD1 and the PCK rat is an orthologous model of disease. Recently, we showed that fibrocystin, Pkhd1 protein, is localized to primary cilia in rat cholangiocytes and that disruption of its ciliary expression results in biliary cystogenesis. This study describes biliary phenotype in the PCK rat using micro-computed tomography scanning and three-dimensional reconstruction, and light, scanning, and transmission microscopy. Our results show that the biliary tree undergoes extensive remodeling resulting in bile duct dilatation, focal budding, and formation of cysts that are initially connected to bile ducts, but throughout time separate from them. Progressive liver enlargement results from massive cyst formation while liver parenchymal volume remains unchanged. Cilia in cystic cells are abnormal consistent with the notion that the primary defect in ARPKD resulting in cystogenesis may be linked to ciliary dysfunction. Our results suggest that the PCK rat is a useful model for studies of biliary cystogenesis and treatment options of inherited cystic liver disease.

Original languageEnglish (US)
Pages (from-to)1719-1730
Number of pages12
JournalAmerican Journal of Pathology
Volume165
Issue number5
StatePublished - Nov 2004

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Autosomal Recessive Polycystic Kidney
Cilia
Liver
Bile Ducts
Cysts
Polycystic Kidney Diseases
Biliary Tract
Liver Diseases
Dilatation
Microscopy
Tomography
Morbidity
Phenotype
Light
Mutation
Mortality
Proteins

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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Biliary dysgenesis in the PCK rat, an orthologous model of autosomal recessive polycystic kidney disease. / Masyuk, Tatyana V.; Huang, Bing Q.; Masyuk, Anatoliy I.; Ritman, Erik L.; Torres, Vicente; Wang, Xiaofang; Harris, Peter C; La Russo, Nicholas F.

In: American Journal of Pathology, Vol. 165, No. 5, 11.2004, p. 1719-1730.

Research output: Contribution to journalArticle

Masyuk, Tatyana V. ; Huang, Bing Q. ; Masyuk, Anatoliy I. ; Ritman, Erik L. ; Torres, Vicente ; Wang, Xiaofang ; Harris, Peter C ; La Russo, Nicholas F. / Biliary dysgenesis in the PCK rat, an orthologous model of autosomal recessive polycystic kidney disease. In: American Journal of Pathology. 2004 ; Vol. 165, No. 5. pp. 1719-1730.
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