J. Lipid Res.
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Journal of Lipid Research, Vol. 40, 1967-1977, November 1999
Copyright © 1999 by Lipid Research, Inc.


Original Article

Apolipoprotein B-related gene expression and ultrastructural characteristics of lipoprotein secretion in mouse yolk sac during embryonic development

Yuko Terasawaa,e, Sylvaine J. Casesa,b, Jinny S. Wongb,d, Haris Jamilh, Sumana Jothif, Maret G. Traberg, Lester Packerf, David A. Gordonh, Robert L. Hamiltonb,d, and Robert V. Farese, Jr.a,c
a Gladstone Institute of Cardiovascular Disease, University of California, San Francisco, CA 94110
b Cardiovascular Research Institute, University of California, San Francisco, CA 94110
c Departments of Medicine, University of California, San Francisco, CA 94110
d Anatomy, University of California, San Francisco, CA 94110
e Departments of Nutritional Sciences, University of California, Berkeley, CA 94720
f Molecular and Cell Biology, University of California, Berkeley, CA 94720
g Linus Pauling Institute, Oregon State University, Corvallis, OR 97331
h Bristol-Myers Squibb, Princeton, NJ 08543

Correspondence to: Robert V. Farese, Jr.

In mice, the yolk sac appears to play a crucial role in nourishing the developing embryo, especially during embryonic days (E) 7;–10. Lipoprotein synthesis and secretion may be essential for this function: embryos lacking apolipoprotein (apo) B or microsomal triglyceride transfer protein (MTP), both of which participate in the assembly of triglyceride-rich lipoproteins, are apparently defective in their ability to export lipoproteins from yolk sac endoderm cells and die during mid-gestation. We therefore analyzed the embryonic expression of apoB, MTP, and {alpha}-tocopherol transfer protein ({alpha}-TTP), which have been associated with the assembly and secretion of apoB-containing lipoproteins in the adult liver, at different developmental time points. MTP expression or activity was found in the yolk sac and fetal liver, and low levels of activity were detected in E18.5 placentas. {alpha}-TTP mRNA and protein were detectable in the fetal liver, but not in the yolk sac or placenta. Ultrastructural analysis of yolk sac visceral endoderm cells demonstrated nascent VLDL within the luminal spaces of the rough endoplasmic reticulum and Golgi apparatus at E7.5 and E8.5. The particles were reduced in diameter at E13.5 and reduced in number at E18.5;–19.

The data support the hypothesis that the yolk sac plays a vital role in providing lipids and lipid-soluble nutrients to embryos during the early phases (E7;–10) of mouse development.—Terasawa, Y., S. J. Cases, J. S. Wong, H. Jamil, S. Jothi, M. G. Traber, L. Packer, D. A. Gordon, R. L. Hamilton, and R. V. Farese, Jr. Apolipoprotein B-related gene expression and ultrastructural chracteristics of lipoprotein secretion in mouse yolk sac during embryonic development. J. Lipid Res. 1999. 40: 1967;–1977.

Supplementary key words: microsomal triglyceride transfer protein, {alpha}-tocopherol transfer protein, vitamin E


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