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

Abstract

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 α-tocopherol transfer protein (α-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. α-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. 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 α-tocopherol transfer protein (α-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. α-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. Vertebrate animals have evolved widely different strategies to nourish developing embryos (1Mossman H.W. Vertebrate Fetal Membranes. New Brunswick, NJ1987Google Scholar). All species possess a yolk sac, but its function and morphology vary greatly. In many species, the yolk sac encloses and subsequently absorbs a yolk containing a variety of proteinaceous and lipid substances, which provide structural materials and fuel for the developing embryo. In addition, blood islands found in the yolk sac play a role in early hematopoeisis. Several mammals, including rodents, rabbits, moles, shrews, armadillos, and some bats, have yolk sacs whose absorptive surface is partially or completely “inverted” (1Mossman H.W. Vertebrate Fetal Membranes. New Brunswick, NJ1987Google Scholar). In such cases, the absorptive surface faces the surrounding uterine decidual tissue, where it is thought to be important in the absorption of maternal nutrients during the early phases of development. This nutritive function precedes and is probably prerequisite for the establishment of the embryo's circulation and chorioallantoic placentation, which subsequently contribute to both nutrient and respiratory functions. In mice, the yolk sac develops around embryonic day (E) 7 and probably plays a vital nutritive role until at least E9–10, when placental function is established. Recent evidence has indicated that lipoprotein synthesis and secretion may be important functions of the mouse yolk sac visceral endoderm. Mouse embryos lacking apolipoprotein (apo) B, the chief structural component of triglyceride-rich lipoproteins, usually die around E8.5–10.5 (2Farese Jr., R.V. Ruland S.L. Flynn L.M. Stokowski R.P. Young S.G. Knockout of the mouse apolipoprotein B gene results in embryonic lethality in homozygotes and protection against diet-induced hypercholesterolemia in heterozygotes.Proc. Natl. Acad. Sci. USA. 1995; 92: 1774-1778Google Scholar, 3Huang L-S. Voyiaziakis E. Markenson D.F. Sokol K.A. Hayek T. Breslow J.L. Apo B gene knockout in mice results in embryonic lethality in homozygotes and neural tube defects, male infertility, and reduced HDL cholesterol ester and apo A-I transport rates in heterozygotes.J. Clin. Invest. 1995; 96: 2152-2161Google Scholar), and the few that survive to later stages are often exencephalic (2Farese Jr., R.V. Ruland S.L. Flynn L.M. Stokowski R.P. Young S.G. Knockout of the mouse apolipoprotein B gene results in embryonic lethality in homozygotes and protection against diet-induced hypercholesterolemia in heterozygotes.Proc. Natl. Acad. Sci. USA. 1995; 92: 1774-1778Google Scholar). Further, gene-targeted embryos capable of synthesizing only low levels of truncated apoB species often have neural tube–related developmental defects, including exencephaly and hydrocephaly (4Homanics G.E. Maeda N. Traber M.G. Kayden H.J. Dehart D.B. Sulik K.K. Exencephaly and hydrocephaly in mice with targeted modification of the apolipoprotein B (Apob) gene.Teratology. 1995; 51: 1-10Google Scholar, 5Homanics G.E. Smith T.J. Zhang S.H. Lee D. Young S.G. Maeda N. Targeted modification of the apolipoprotein B gene results in hypobetalipoproteinemia and developmental abnormalities in mice.Proc. Natl. Acad. Sci. USA. 1993; 90: 2389-2393Google Scholar, 6Kim E. Cham C.M. Véniant M.M. Ambroziak P. Young S.G. Dual mechanisms for the low plasma levels of truncated apolipoprotein B proteins in familial hypobetalipoproteinemia. Analysis of a new mouse model with a nonsense mutation in the Apob gene.J. Clin. Invest. 1998; 101: 1468-1477Google Scholar). A similar phenotype was observed decades ago in rat embryos deficient in vitamin E (7Urner J.A. The intra-uterine changes in the pregnant albino rat (Mus norvegicus) deprived of vitamin E.Anat. Rec. 1931; 50: 175-187Google Scholar, 8Verma K. King D.W. Disorders of the developing nervous system of vitamin E-deficient rats.Acta Anat. 1967; 67: 623-635Google Scholar, 9Cheng D.W. Chang L.F. Bairnson T.A. Gross observations on developing abnormal embryos induced by maternal vitamin E deficiency.Anat. Rec. 1957; 129: 167-185Google Scholar). Indeed, α-tocopherol is undetectable in E9.5 mouse embryos lacking apoB (10Farese Jr., R.V. Cases S. Ruland S.L. Kayden H.J. Wong J.S. Young S.G. Hamilton R.L. A novel function for apolipoprotein B: lipoprotein synthesis in the yolk sac is critical for maternal–fetal lipid transport in mice.J. Lipid Res. 1996; 37: 347-360Google Scholar). These observations led us to hypothesize that the yolk sac endoderm synthesizes and secretes apoB-containing lipoproteins during the early stages of embryonic development. To test this hypothesis, ultrastructural analysis of yolk sac cells from E9.5 embryos and demonstrated low lipoprotein lipoprotein particles in the endoplasmic Golgi and (10Farese Jr., R.V. Cases S. Ruland S.L. Kayden H.J. Wong J.S. Young S.G. Hamilton R.L. A novel function for apolipoprotein B: lipoprotein synthesis in the yolk sac is critical for maternal–fetal lipid transport in mice.J. Lipid Res. 1996; 37: 347-360Google Scholar). In particles were in yolk sac endoderm which therefore lipid at their a model (10Farese Jr., R.V. Cases S. Ruland S.L. Kayden H.J. Wong J.S. Young S.G. Hamilton R.L. A novel function for apolipoprotein B: lipoprotein synthesis in the yolk sac is critical for maternal–fetal lipid transport in mice.J. Lipid Res. 1996; 37: 347-360Google in which the absorptive surface of the yolk sac endoderm cells absorbs lipids and lipid-soluble nutrients from the maternal decidual or maternal lipids at the surface of the endoderm and both lipids and lipid-soluble nutrients and lipids apoB-containing These lipoproteins are from the surface of endoderm cells for transport to the developing embryo, by or the This model of yolk lipoprotein secretion that crucial to the assembly of apoB-containing lipoproteins are essential for embryonic in This was for microsomal triglyceride transport protein (MTP), a microsomal protein that is in the and and is thought to participate in the of nascent apoB-containing particles A. M. J. G. of microsomal triglyceride transfer protein in with Scholar). with in the MTP gene have of apoB-containing lipoproteins in and have to vitamin E D. L. K.A. K. C.M. and gene in microsomal triglyceride transfer protein associated with 1993; Scholar, A. S. S. P. J. is by of the gene the of a microsomal triglyceride transfer 1993; Scholar). The that the mouse yolk sac MTP at and that mice for MTP gene die at M. Flynn L.M. Wong J.S. Véniant M.M. Hamilton R.L. Young S.G. Knockout of the gene in lipoprotein secretion in and embryonic lethality in Natl. Acad. Sci. USA. 1998; the of the synthesis and secretion of apoB-containing lipoproteins during early stages of mouse To lipoprotein assembly and secretion by the yolk sac during embryonic analyzed the expression of apoB, MTP, and α-tocopherol transfer protein (α-TTP), of which are associated with the assembly and secretion of apoB-containing lipoproteins in the adult liver, at different time of embryonic development. α-TTP is a protein in of H. A. S. K. T. K. of α-tocopherol transfer protein from rat with 1993; and M. A. T. E. Kayden H.J. H. K. α-tocopherol transfer expression and J. 1995; Scholar), where it is thought to the of α-tocopherol apoB-containing nascent VLDL the plasma M.G. Sokol A. T. R. Kayden H.J. of α-tocopherol in with familial vitamin E Lipid Res. 1993; Scholar, M.G. Kayden H.J. and are in but is in low Lipid Res. Scholar, M.G. Sokol Kayden H.J. ability of with familial vitamin E to α-tocopherol lipoproteins by the Clin. Invest. Scholar), the for this not to of nascent VLDL M. K. H. K. transfer protein the secretion of α-tocopherol from a a Natl. Acad. Sci. USA. Traber and R. Hamilton, with in the α-TTP gene have vitamin E and abnormalities K. M. Kayden H. Sokol R. H. K. M. with vitamin E is by in the α-tocopherol transfer 1995; Scholar, A. M. R. T. α-tocopherol transfer and in familial vitamin E 1996; Scholar, L. K. Kayden H.J. S. L. M. with vitamin E of and in a number of J. 1998; Scholar). gene expression in the adult and the visceral yolk sac endoderm are similar of protein gene expression in mouse visceral yolk sac and J. and the phenotype of apoB that of vitamin E in rodents, that α-TTP may be in the yolk sac or embryonic during development. the ultrastructural of the yolk sac endoderm by at early and stages of to this with to the and of lipoproteins during development. mice were in a with a and and to Mouse and were from and of A Scholar). expression in embryos embryonic and were and E9.5 and yolk sac embryonic were by for and protein analysis were and in and at until was from with to the was from of with and a was with of the and mouse the (10Farese Jr., R.V. Cases S. Ruland S.L. Kayden H.J. Wong J.S. Young S.G. Hamilton R.L. A novel function for apolipoprotein B: lipoprotein synthesis in the yolk sac is critical for maternal–fetal lipid transport in mice.J. Lipid Res. 1996; 37: 347-360Google a mouse apoB, the is on and the is on (10Farese Jr., R.V. Cases S. Ruland S.L. Kayden H.J. Wong J.S. Young S.G. Hamilton R.L. A novel function for apolipoprotein B: lipoprotein synthesis in the yolk sac is critical for maternal–fetal lipid transport in mice.J. Lipid Res. 1996; 37: 347-360Google the apoB is mouse MTP, the on and the on containing for that are not in the a the on and on a of or apoB, were for of at at and at MTP and α-TTP were for of at at and at of and of and were in containing and were analyzed by on were in a containing of of of and of of of and of in were at for was and the was at for were on The mouse apoB is a from the of (10Farese Jr., R.V. Cases S. Ruland S.L. Kayden H.J. Wong J.S. Young S.G. Hamilton R.L. A novel function for apolipoprotein B: lipoprotein synthesis in the yolk sac is critical for maternal–fetal lipid transport in mice.J. Lipid Res. 1996; 37: 347-360Google Scholar). The a of and a apoB of The mouse MTP is a from the of the that results in a of The mouse α-TTP was a containing by the in the the α-TTP is and the is The by of was a mouse M. Flynn L.M. Wong J.S. Véniant M.M. Hamilton R.L. Young S.G. Knockout of the gene in lipoprotein secretion in and embryonic lethality in Natl. Acad. Sci. USA. 1998; the is and the is protection were with the to the of was with of for apoB and for MTP and in at was by for at were and the was were at for in and in a were on and to for were with a and expression was a to for M. Flynn L.M. Wong J.S. Véniant M.M. Hamilton R.L. Young S.G. Knockout of the gene in lipoprotein secretion in and embryonic lethality in Natl. Acad. Sci. USA. 1998; Scholar, D. G. In of lipoprotein by at the in rat and J. 1993; Scholar). MTP was A. M. J. G. of microsomal triglyceride transfer protein in with Scholar). were to and to MTP was detected with that the component of MTP A. M. J. G. of microsomal triglyceride transfer protein in with Scholar). α-TTP a was against the of the rat α-TTP H. A. S. K. T. K. of α-tocopherol transfer protein from rat with 1993; Scholar). This detected a protein in mouse were to and to The was with a of the and with a and detected with MTP activity on of triglyceride from to were with of protein A. M. J. G. of microsomal triglyceride transfer protein in with Scholar). were in and with a R.L. Wong J.S. Cham C.M. Young S.G. lipid particles are in the of apolipoprotein B Lipid Res. 1998; that of (10Farese Jr., R.V. Cases S. Ruland S.L. Kayden H.J. Wong J.S. Young S.G. Hamilton R.L. A novel function for apolipoprotein B: lipoprotein synthesis in the yolk sac is critical for maternal–fetal lipid transport in mice.J. Lipid Res. 1996; 37: 347-360Google Scholar, R.L. Wong J.S. Cham C.M. Young S.G. lipid particles are in the of apolipoprotein B Lipid Res. 1998; Scholar). E7.5 and time embryos were from or in the decidual in the a was in the to of the In gene expression for apoB, MTP, and α-TTP on from embryos at early or stages of development. E7.5 embryos are analyzed expression from of the E13.5 and E18.5 time analyzed expression in the yolk sac, and embryonic this were to for of the gene at detectable levels for of the The levels of apoB were in the yolk sac and the levels of α-TTP were in fetal MTP were detected in To the expression of from embryonic at different developmental time points. expression was detected at E7.5 and was at levels in the yolk sac at E13.5 and E18.5 and at levels in embryonic at both time apoB expression was in yolk sac the in of apoB expression were detected in E18.5 placenta. for apoB expression in the yolk sac was that in adult but that in adult The MTP expression by was similar to that for apoB MTP expression was detected at E7.5 and was at levels in the yolk sac at E13.5 and E18.5 the in the and at levels in embryonic at both time points. MTP mRNA expression was not observed in the placenta. was the for apoB, MTP was at levels in the yolk sac in adult α-TTP expression was detectable in E18.5 liver, but at a in adult α-TTP expression was not detectable in placenta. In the in not α-TTP expression in the yolk sac of levels of from the apoB We therefore to α-TTP expression A of the low levels of α-TTP expression in the fetal at E13.5 and but not expression in the yolk sac at time were to MTP and α-TTP protein with that the component of MTP A. M. J. G. of microsomal triglyceride transfer protein in with demonstrated MTP protein in yolk but not placental tissue, of E13.5 embryos of MTP protein were detected in fetal from this time and not analysis of demonstrated that the of MTP protein in the yolk sac was the found in adult mouse and with against a from the rat α-TTP demonstrated expression levels of the protein in from the adult mouse and low expression levels in E18.5 levels of α-TTP expression were observed in E13.5 α-TTP protein was not detected in the yolk sac or at time protein expression in embryonic were to to and with that similar of proteins in To the and expression of MTP MTP in embryonic at different developmental time MTP activity was in from E7.5 and and in and E18.5 yolk in MTP activity was in yolk sac the in from the MTP activity was in E13.5 and E18.5 MTP activity levels in E13.5 were similar to in but were in E18.5 on yolk sacs from and The ultrastructural analysis of E7.5 yolk sac endoderm nascent VLDL assembly and secretion by in within the These particles were within the of the rough endoplasmic reticulum in the Golgi were in within this early time not of the visceral yolk sac cells to be nascent visceral yolk sac nascent VLDL particles within the of the and Golgi and particles were of VLDL diameter of yolk sac visceral endoderm cells particles of VLDL within and within on the Golgi The ultrastructural of yolk sac visceral endoderm VLDL secretion to be similar at and E9.5 (4Homanics G.E. Maeda N. Traber M.G. Kayden H.J. Dehart D.B. Sulik K.K. Exencephaly and hydrocephaly in mice with targeted modification of the apolipoprotein B (Apob) gene.Teratology. 1995; 51: 1-10Google Scholar). nascent VLDL particles were in diameter at but to be or especially in cells to the the particles were in diameter and reduced in in that some visceral yolk sac from the to or In cells the of particles were observed in in the Golgi particles of the were observed in the spaces at the of the yolk sac visceral and endoderm of yolk sac visceral endoderm at in apoB-containing lipoproteins within of the Golgi apparatus and in the spaces at the of the yolk sac visceral and endoderm. of their lipoproteins are with observations in rat yolk sac Recent in the role of the microsomal triglyceride transfer protein in apolipoprotein B lipoprotein Scholar), in which was in particles of This that gene associated with the adult assembly and secretion of apoB-containing lipoproteins, MTP and are in the developing mouse embryo. MTP was at developmental time with the levels in the yolk sac by fetal in was only in the fetal The ultrastructural evidence that lipoprotein assembly and secretion by the yolk sac in cells by E7.5 and are in visceral cells at by the of particles within the lipoprotein secretion with many or particles in the the particles were of the of of the particles to be and their in some cells from the to These data support the model have (10Farese Jr., R.V. Cases S. Ruland S.L. Kayden H.J. Wong J.S. Young S.G. Hamilton R.L. A novel function for apolipoprotein B: lipoprotein synthesis in the yolk sac is critical for maternal–fetal lipid transport in mice.J. Lipid Res. 1996; 37: 347-360Google in which lipoprotein synthesis and secretion by the yolk sac play vital in the early (E7–10) stages of mouse development. embryos and a time of that precedes the establishment of a this early the yolk sac visceral endoderm is thought to nutrients for the developing in a similar to that in adult This early function of the yolk sac is probably critical until the later establishment of a placental the of gene expression in the yolk sac is similar to that of the of protein gene expression in mouse visceral yolk sac and J. Scholar), that both MTP and gene that have been associated with lipoprotein assembly and secretion in the liver, may be in the yolk MTP was in the yolk sac, demonstrated by of expression at the and activity This was in with a by M. Flynn L.M. Wong J.S. Véniant M.M. Hamilton R.L. Young S.G. Knockout of the gene in lipoprotein secretion in and embryonic lethality in Natl. Acad. Sci. USA. 1998; in their of MTP knockout We observed levels of MTP protein and activity at the early and of with role in providing of nascent apoB-containing lipoproteins Recent in the role of the microsomal triglyceride transfer protein in apolipoprotein B lipoprotein Scholar). expression of both MTP and apoB was in yolk sac the in from the placenta. The yolk sac the is and and function of the of Scholar), and it in lipid transport at developmental time points. with this structural and ultrastructural demonstrated of lipoprotein particles in cells from the placenta. In to the of apoB expression in rat at J. expression and developmental of the rat apolipoprotein B Natl. Acad. Sci. USA. Scholar), found only of apoB expression in E18.5 mouse placenta. In to MTP, α-TTP expression was not detected in the yolk sac, when by α-TTP mRNA and were detectable at low levels in the fetal The of expression in the yolk sac and the of α-TTP in the fetal are of the in the adult and the adult not α-TTP H. A. S. K. T. K. of α-tocopherol transfer protein from rat with 1993; and of vitamin the adult and this expression to the of lipoproteins in the α-tocopherol of vitamin E. In the embryo, the yolk sac may be with to vitamin E and the embryonic may contribute to of lipoproteins in the with a function be important vitamin E is critical for (7Urner J.A. The intra-uterine changes in the pregnant albino rat (Mus norvegicus) deprived of vitamin E.Anat. Rec. 1931; 50: 175-187Google Scholar, 9Cheng D.W. Chang L.F. Bairnson T.A. Gross observations on developing abnormal embryos induced by maternal vitamin E deficiency.Anat. Rec. 1957; 129: 167-185Google Scholar). A knockout of the α-TTP gene in mice to this ultrastructural observations are with the role of the yolk sac during the the ultrastructural morphology of E9.5 yolk sac visceral endoderm for the time that this and secretes particles at this early time (10Farese Jr., R.V. Cases S. Ruland S.L. Kayden H.J. Wong J.S. Young S.G. Hamilton R.L. A novel function for apolipoprotein B: lipoprotein synthesis in the yolk sac is critical for maternal–fetal lipid transport in mice.J. Lipid Res. 1996; 37: 347-360Google Scholar). In the observed evidence of lipoprotein assembly of lipoproteins in endoderm cells early E7.5 and VLDL particles at both and The VLDL of lipoproteins results from the of of during their MTP activity was at levels at time points. The ultrastructural of nascent VLDL in the of yolk sac cells in important from that in adult where particles are found in the In the VLDL are found only at the of the and in the Hamilton R.L. of B of plasma lipoproteins in rat Scholar). the stages of lipoprotein to be indicated by the of but the of the lipoproteins were This this to the time when the of MTP activity were observed in the yolk the of apoB to MTP mRNA expression was at E13.5 at the time which with the of lipid The data at E13.5 be with a in the transport of but a of for this from in the developing where the yolk sac endoderm secretes of apoB-containing VLDL for transport to the developing M. Lipid and the Lipid Res. Scholar). In a of H. D. L. R. secretion and of apolipoprotein lipoprotein particles in the visceral rat yolk and D. L. H. R. The visceral yolk important of synthesis and secretion of apolipoprotein B containing lipoproteins in the of the Scholar, D. A. R. The of apolipoprotein containing lipoprotein by the visceral rat yolk sac on developmental and 1996; have the of rat yolk sac endoderm lipoprotein secretion and the of lipoproteins by yolk These observed in in yolk sac lipoprotein was on the day of on and was on D. A. R. The of apolipoprotein containing lipoprotein by the visceral rat yolk sac on developmental and 1996; Scholar). observed that particles were by rat yolk sac their observations were at time D. A. R. The of apolipoprotein containing lipoprotein by the visceral rat yolk sac on developmental and 1996; Scholar). their observations in are with observations of diameter particles in mice at later developmental time points. We that particles are by yolk sac endoderm in rat embryos at time points. The vital of lipoprotein by yolk sac endoderm in developing mouse embryos the of which essential nutrients are many on lipoproteins, such cholesterol or essential and or vitamin E or vitamin of the in of mouse embryos lacking apoB and rat of vitamin E (7Urner J.A. The intra-uterine changes in the pregnant albino rat (Mus norvegicus) deprived of vitamin E.Anat. Rec. 1931; 50: 175-187Google Scholar, 8Verma K. King D.W. Disorders of the developing nervous system of vitamin E-deficient rats.Acta Anat. 1967; 67: 623-635Google Scholar, 9Cheng D.W. Chang L.F. Bairnson T.A. Gross observations on developing abnormal embryos induced by maternal vitamin E deficiency.Anat. Rec. 1957; 129: 167-185Google Scholar), the lethality observed in embryos may at least in to vitamin E the of apoB-containing lipoproteins may in a nutritive of lipids in to vitamin this is by the role of cholesterol in in Jr., R.V. J. and 1998; Scholar), which have a role for cholesterol in important developmental the protein J.A. Young modification of proteins in 1996; Scholar). In this have the mouse yolk sac endoderm a of in apoB-containing lipoproteins are essential for the of mouse and rat adult survive with a of apoB-containing lipoproteins Jr., R.V. Young S.G. Lipid Res. 1993; Scholar). deficient in MTP or α-TTP have been D. L. K.A. K. C.M. and gene in microsomal triglyceride transfer protein associated with 1993; Scholar, A. S. S. P. J. is by of the gene the of a microsomal triglyceride transfer 1993; Scholar, K. M. Kayden H. Sokol R. H. K. M. with vitamin E is by in the α-tocopherol transfer 1995; Scholar, A. M. R. T. α-tocopherol transfer and in familial vitamin E 1996; Scholar). of of gene in developmental abnormalities have not been and the that to vitamin E in evidence is apoB-containing lipoprotein by the yolk sac may not be critical for This be to different embryonic nutrient or maternal–fetal transport The placental circulation is early during and the transport mechanisms for lipids in the and lipid may be different from in the mouse yolk We and for and for and for in This was by from the the J. and of the and the of and and of apolipoprotein embryonic day endoplasmic reticulum microsomal triglyceride transfer protein rough endoplasmic reticulum α-tocopherol transfer protein low