A novel function for apolipoprotein B: lipoprotein synthesis in the yolk sac is critical for maternal-fetal lipid transport in mice.
Apolipoprotein (apo) B, the principal structural component necessary for the synthesis and secretion of triglyceride-rich lipoproteins by the intestine and liver, is highly expressed in the yolk sac visceral endoderm of mammals, although its function in this tissue has been hitherto unclear. Disruption of the apoB gene in mice results in embryonic lethality (approximately 9.5 - 10.5 d). Here we demonstrate that apoB is normally expressed at early time points in embryonic development in yolk sac visceral endodermal cells, and that this expression is associated with the synthesis and secretion of apoB-containing lipoproteins. The lack of apoB in the visceral endoderm resulted in an accumulation of intracellular lipid droplets, an absence of lipoproteins from the secretory pathway, and reduced concentrations of cholesterol and alpha-tocopherol in tissues of apoB-/- embryos. Visceral endoderm of apoB+/- embryos exhibited an intermediate phenotype. Our results suggest that apoB plays an essential role in the transport of lipid nutrients to the developing mouse embryo via the yolk sac-mediated synthesis and secretion of apoB-containing lipoproteins.
Farese
R V
RV
Gladstone Institute of Cardiovascular Disease, San Francisco, CA 94141-9100, USA.
Cases
S
S
Ruland
S L
SL
Kayden
H J
HJ
Wong
J S
JS
Young
S G
SG
Hamilton
R L
RL
D000818:Animals; D001055:Apolipoproteins B / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D001483:Base Sequence; D004707:Endoderm / Q000378:metabolism / Q000648:ultrastructure; D005260:Female; D015870:Gene Expression; D050356:Lipid Metabolism; D008074:Lipoproteins / Q000096:biosynthesis*; D008431:Maternal-Fetal Exchange / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008854:Microscopy, Electron; D008969:Molecular Sequence Data; D011247:Pregnancy; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D015017:Yolk Sac / Q000378:metabolism* / Q000648:ultrastructure
D001055:Apolipoproteins B; D008074:Lipoproteins; D012333:RNA, Messenger