title: Intestinal bile salt absorption in Atp8b1 deficient mice.
abstract: OBJECTIVE
  Mutations in the ATP8B1 gene can cause Progressive Familial Intrahepatic Cholestasis type 1. We have previously reported that Atp8b1(G308V/G308V) mice, a model for PFIC1, have slightly, but significantly, higher baseline serum bile salt (BS) concentrations compared to wt mice. Upon BS feeding, serum BS concentrations strongly increased in Atp8b1-deficient mice. Despite these findings, we observed only mildly impaired canalicular BS transport. In the present report we tested the hypothesis that Atp8b1(G308V/G308V) mice hyperabsorb BS in the intestine during BS feeding.
  
  
  METHODS
  Intestinal BS absorption was measured in intestinal perfusion and in intestinal explants. In addition, we measured BS concentrations in portal blood. Ileal expression of the Fxr-targets Asbt, Ilbp and Shp was assessed.
  
  
  RESULTS
  In wt and Atp8b1(G308V/G308V) mice, intestinal taurocholate absorption is primarily mediated by the ileal bile salt transporter Asbt. Neither of the experimental systems revealed enhanced absorption of BS in Atp8b1(G308V/G308V) mice compared to wt mice. In line with these observations, we found no difference in the ileal protein expression of Asbt. Induction of Shp expression during BS feeding also demonstrated that Fxr signalling is intact in Atp8b1(G308V/G308V) mice.
  
  
  CONCLUSIONS
  The accumulation of BS in plasma of Atp8b1(G308V/G308V) mice during BS feeding is not caused by increased intestinal BS absorption.
authors: AMC Liver Center, Academic Medical Center, Room S1-166, Meibergdreef 69-71, 1105 BK Amsterdam, The Netherlands.
authors: Annemiek
authors: A
authors: Groen
authors: Cindy
authors: C
authors: Kunne
authors: Coen C
authors: CC
authors: Paulusma
authors: Werner
authors: W
authors: Kramer
authors: Luis B
authors: LB
authors: Agellon
authors: Laura N
authors: LN
authors: Bull
authors: Ronald P J
authors: RP
authors: Oude Elferink
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics*; D000818:Animals; D001647:Bile Acids and Salts / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism*; D020355:Cholates / Q000008:administration & dosage; D002780:Cholestasis, Intrahepatic / Q000235:genetics; D004268:DNA-Binding Proteins / Q000378:metabolism; D004032:Diet; D004195:Disease Models, Animal; D005346:Fibroblast Growth Factors / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D007408:Intestinal Absorption / Q000235:genetics / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D029363:Organic Anion Transporters, Sodium-Dependent / Q000378:metabolism; D010477:Perfusion; D049294:Phospholipid Transfer Proteins; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D015398:Signal Transduction; D027981:Symporters / Q000378:metabolism; D013656:Taurocholic Acid / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D000099150:Receptor, Farnesoid X-Activated
chemical_list: D000251:Adenosine Triphosphatases; D001647:Bile Acids and Salts; D020355:Cholates; D004268:DNA-Binding Proteins; D005346:Fibroblast Growth Factors; D029363:Organic Anion Transporters, Sodium-Dependent; D049294:Phospholipid Transfer Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D027981:Symporters; D013656:Taurocholic Acid; D014157:Transcription Factors; D000099150:Receptor, Farnesoid X-Activated; C108526:fibroblast growth factor 15, mouse; C071908:sodium-bile acid cotransporter; C491742:Atp8b1 protein, mouse