Abstract
Mutations in ATP8B1 are associated with FIC1 disease, an autosomal recessive disorder in which intrahepatic cholestasis is the predominant manifestation. ATP8B1 encodes FIC1, which is expressed in several tissues, most prominently in the intestine, pancreas, and stomach and, to a much lesser extent, in the liver. In this study, Fic1 localization and expression during postnatal development was examined in healthy mice. Immunoblot and RT-PCR analysis indicated Fic1 is expressed abundantly in regions of the adult gastrointestinal tract of humans and mice. Immunohistochemistry revealed that Fic1 was localized to the apical membranes of enterocytes, pancreatic acinar cells, gastric pit epithelial cells, and hepatocytes and cholangiocytes. Subsequent analysis of early postnatal expression revealed that Fic1 expression in the small intestine was limited or absent at the age of 7 and 14 d and increased significantly with maturation. In contrast, pancreatic, hepatic, and gastric Fic1 expression was not diminished during the first 3 wk of postnatal development. In conclusion, these data show that Fic1 is expressed in a tissue-specific and developmentally regulated fashion at the apical membranes of epithelial cells. We speculate that the developing bile salt pool in the maturing intestine accounts for the increase in Fic1 protein expression in this tissue.
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Abbreviations
- ASBT:
-
apical sodium-dependent bile salt transporter
- BRIC:
-
benign recurrent intrahepatic cholestasis
- FIC1:
-
familial intrahepatic cholestasis 1
- GFC:
-
Greenland familial cholestasis
- GGT:
-
γ-glutamyltranspeptidase
- IBABP:
-
ileal bile acid binding protein
- PFIC1:
-
progressive familial intrahepatic cholestasis type 1
- SCHAD:
-
short chain L-3-hydroxyacyl-CoA
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Acknowledgements
The authors thank Dr. J. Dekker (Erasmus University Rotterdam, the Netherlands) for gifts of the antilactase antibodies, Prof. Dr. R.P.J. Oude Elferink (Academic Medical Center, Amsterdam) for valuable discussions, and Dr. A.E.M. Klomp for critical evaluation of this manuscript.
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Supported by Grant WS98-12 of the Dutch Digestive Disease Foundation (L.W.J.K., S.W.C.v.M.).
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van Mil, S., van Oort, M., van den Berg, I. et al. FIC1 Is Expressed at Apical Membranes of Different Epithelial Cells in the Digestive Tract and Is Induced in the Small Intestine During Postnatal Development of Mice. Pediatr Res 56, 981–987 (2004). https://doi.org/10.1203/01.PDR.0000145564.06791.D1
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DOI: https://doi.org/10.1203/01.PDR.0000145564.06791.D1
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