Defects in cholangiocyte fibrocystin expression and ciliary structure in the @entity23887 XXXX .

@entity23887 @entity8 @entity96 @entity70956 @entity35 @entity1125
BACKGROUND _ AIMS: Recent studies have showed that proteins associated with @entity8 ( @entity8 ) are expressed in cilia, linking this organelle and cyst formation in the kidney, but involvement of cilia in @entity8 -related biliary cystogenesis has not been shown. We investigated: (1) the expression of fibrocystin (a product of @entity70956 , the @entity8 [ @entity8 ] gene) in cholangiocyte cilia; (2) @entity1125 formation in an orthologous @entity35 model, @entity23887 ; and (3) the effect of @entity70956 mutation on ciliary structure. METHODS: Biliary cystogenesis was assessed by microcomputed tomography. Fibrocystin expression in cholangiocytes of isolated intrahepatic bile ducts (IBDUs) and @entity96 was analyzed by confocal and immunoelectron microscopy, and ciliary structure and length by scanning and transmission electron microscopy. Small interfering RNAs (siRNA) were used to examine the effect of fibrocystin loss on ciliary structure. RESULTS: The biliary tree in the @entity23887 @entity35 was distorted markedly, showing multiple bile duct dilatation and focal budding. In normal IBDUs, each cholangiocyte had a single cilium that expressed fibrocystin. In contrast, cilia in the @entity23887 @entity35 were abnormal with bulbous extensions and diminished length, and were devoid of fibrocystin. In cholangiocytes of normal IBDUs, specific siRNA reduced @entity70956 messenger RNA by 80%, the length of cilia by 41%, and fibrocystin ciliary expression to an undetectable level. CONCLUSIONS: Our results indicate that fibrocystin is expressed in cholangiocyte cilia and that disruption of @entity70956 by a germ line mutation in the @entity23887 @entity35 or by siRNA in IBDUs results in abnormalities in ciliary morphology and possibly biliary cystogenesis.
