Homozygous disruption of the murine MDR2 P-glycoprotein gene leads to a complete absence of phospholipid from bile and to liver disease

J. J M Smit, A. H. Schinkel, R. P J Oude Elferink, A. K. Groen, E. Wagenaar, L. van Deemter, C. A A M Mol, R. Ottenhoff, N. M T van der Lugt, M. A. van Roon, M. A. van der Valk, G. J A Offerhaus, A. J M Berns, P. Borst

Research output: Contribution to journalArticle

Abstract

Two types of P-glycoprotein have been found in mammals: the drug-transporting P-glycoproteins and a second type, unable to transport hydrophobic anticancer drugs. The latter is encoded by the human MDR3 (also called MDR2) and the mouse mdr2 genes, and its tissue distribution (bile canalicular membrane of hepatocytes, B cells, heart, and muscle) suggests a specialized metabolic function. We have generated mice homozygous for a disruption of the mdr2 gene. These mice develop a liver disease that appears to be caused by the complete inability of the liver to secrete phospholipid into the bile. Mice heterozygous for the disrupted allele had no detectable liver pathology, but half the level of phospholipid in bile. We conclude that the mdr2 P-glycoprotein has an essential role in the secretion of phosphatidylcholine into bile and hypothesize that it may be a phospholipid transport protein or phospholipid flippase.

Original languageEnglish (US)
Pages (from-to)451-462
Number of pages12
JournalCell
Volume75
Issue number3
DOIs
StatePublished - Nov 5 1993
Externally publishedYes

    Fingerprint

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

Cite this

Smit, J. J. M., Schinkel, A. H., Elferink, R. P. J. O., Groen, A. K., Wagenaar, E., van Deemter, L., Mol, C. A. A. M., Ottenhoff, R., van der Lugt, N. M. T., van Roon, M. A., van der Valk, M. A., Offerhaus, G. J. A., Berns, A. J. M., & Borst, P. (1993). Homozygous disruption of the murine MDR2 P-glycoprotein gene leads to a complete absence of phospholipid from bile and to liver disease. Cell, 75(3), 451-462. https://doi.org/10.1016/0092-8674(93)90380-9