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.
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.
van Mil
Saskia W C
SW
Department of Pediatric Gastroenterology, University Medical Center Utrecht, 3584 EA Utrecht, The Netherlands.
van Oort
Masja M
MM
van den Berg
Inge E T
IE
Berger
Ruud
R
Houwen
Roderick H J
RH
Klomp
Leo W J
LW
D000251:Adenosine Triphosphatases / Q000235:genetics* / Q000378:metabolism*; D000818:Animals; D001652:Bile Ducts / Q000166:cytology / Q000254:growth & development / Q000502:physiology; D016764:Cell Polarity / Q000502:physiology; D004847:Epithelial Cells / Q000166:cytology / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D007413:Intestinal Mucosa / Q000166:cytology / Q000254:growth & development* / Q000502:physiology*; D007422:Intestines / Q000254:growth & development / Q000502:physiology; D008099:Liver / Q000254:growth & development / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D010179:Pancreas / Q000254:growth & development / Q000502:physiology; D049294:Phospholipid Transfer Proteins; D013270:Stomach / Q000254:growth & development / Q000502:physiology
D049294:Phospholipid Transfer Proteins; D000251:Adenosine Triphosphatases; C491742:Atp8b1 protein, mouse