Mice without phosphatidylcholine transfer protein have no defects in the secretion of phosphatidylcholine into bile or into lung airspaces.
Phosphatidylcholine transfer protein (Pc-tp) is a highly specific carrier of phosphatidylcholine (PC) without known function. Proposed functions include the supply of PC required for secretion into bile or lung air space (surfactant) and the facilitation of enzymatic reactions involving PC synthesis or breakdown. To test these functions, we generated knock-out mice unable to make Pc-tp. Remarkably, these mice are normal and have no defect in any of the postulated Pc-tp functions analyzed. The lipid content and composition of the bile, as well as lung surfactant secretion and composition, of Pc-tp (-/-) mice, is normal. The lack of a Pc-tp contribution to biliary lipid secretion is in agreement with our finding that Pc-tp is down-regulated in adult mouse liver: whereas Pc-tp is abundant in the liver of mouse pups, Pc-tp levels decrease > 10-fold around 2 wk after birth, when bile formation starts. In adult mice, Pc-tp levels are high only in epididymis, testis, kidney, and bone marrow-derived mast cells. Absence of Pc-tp in bone marrow-derived mast cells does not affect their lipid composition or PC synthesis and degradation. We discuss how PC might reach the canalicular membrane of the hepatocyte for secretion into the bile, if not by Pc-tp.
van Helvoort
A
A
Division of Molecular Biology, Center of Biomedical Genetics, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands.
de Brouwer
A
A
Ottenhoff
R
R
Brouwers
J F
JF
Wijnholds
J
J
Beijnen
J H
JH
Rijneveld
A
A
van der Poll
T
T
van der Valk
M A
MA
Majoor
D
D
Voorhout
W
W
Wirtz
K W
KW
Elferink
R P
RP
Borst
P
P
D000595:Amino Acid Sequence; D000727:Androgen-Binding Protein; D000818:Animals; D001646:Bile / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics / Q000502:physiology*; D002478:Cells, Cultured; D018076:DNA, Complementary / Q000032:analysis; D006801:Humans; D015289:Leukotrienes / Q000096:biosynthesis; D008168:Lung / Q000378:metabolism*; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D010713:Phosphatidylcholines / Q000378:metabolism*; D049488:Phosphatidylethanolamine Binding Protein; D049294:Phospholipid Transfer Proteins; D011663:Pulmonary Surfactants / Q000096:biosynthesis
D000727:Androgen-Binding Protein; D002352:Carrier Proteins; D018076:DNA, Complementary; D015289:Leukotrienes; C511482:PEBP1 protein, human; D010713:Phosphatidylcholines; D049488:Phosphatidylethanolamine Binding Protein; D049294:Phospholipid Transfer Proteins; D011663:Pulmonary Surfactants