The syncytin-A envelope gene of retroviral origin is essential for mouse placental development

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BioMed Central Page 1 of 1 (page number not for citation purposes) Retrovirology Open Access Oral presentation The syncytin-A envelope gene of retroviral origin is essential for mouse placental development Anne Dupressoir* 1 , Cécile Vernochet 1 , Olivia Bawa 2 , Francis Harper 3 , Gérard Pierron 3 , Paule Opolon 2 and Thierry Heidmann 1 Address: 1 Unité des Rétrovirus Endogènes et Eléments Rétroïdes des Eucaryotes Supérieurs, UMR 8122 CNRS, Institut Gustave Roussy, Villejuif, France, 2 Vectorologie et Transfert de Gènes, UMR 8121, Institut Gustave Roussy, Villejuif, France and 3 Laboratoire de Réplication de l'ADN et Ultrastructure du Noyau, FRE 2937 Institut André Lwoff, Villejuif, France * Corresponding author In several mammalian species, the fusion of throphoblas- tic cells into a multinucleated syncytiotrophoblast layer - taking place at the fetomaternal interface-constitutes a key process of placenta morphogenesis. In the last years, two pairs of genes of retroviral origin encoding envelope pro- teins were identified in the human (syncytin-1 and -2) [1- 3] and mouse (syncytin-A and -B) [4] genomes. These genes, that were independently acquired through ancient retroviral infections of the primate and muridae lineage, 20 to 40 MYA ago, display the characteristics of potential effectors of the trophoblast fusion process. In fact, syncy- tin genes are specifically expressed in the placenta, at the interhaemal syncytial barrier, display cell-cell fusogenic activity, and have been functionally conserved in evolu- tion. Here, to definitely assess the role of these genes, we gener- ated knockout mice for syncytin-A. We show that homozygous syncytin-A null embryos die in utero between 11.5 and 13.5 days of gestation. Syncytin-A-deficient pla- centae exhibit disruption of the architecture of the syncy- tiotrophoblast-containing labyrinth, with overexpansion of trophoblast cells at the expense of fetal blood vessels spaces, and defects in formation of one of the two interhe- mal syncytial layers. These results demonstrate that syncy- tin-A is essential for placenta development and syncytiotrophoblast morphogenesis, and provide evi- dence that genes captured from ancestral retroviruses have been pivotal in the acquisition of new important func- tions during mammalian evolution. References 1. Mi S, Lee X, Li X, Veldman G, Finnerty H, Racie L, LaVallie E, Tang X, Edouard P, Howes S, Keith JJ, McCoy J: Nature 2000, 17:785-89. 2. Blond JL, Lavillette D, Cheynet V, Bouton O, Oriol G, Chapel-Fern- andes S, Mandrand B, Mallet F, Cosset FL: J Virol 2000, 74:3321-29. 3. Blaise S, de Parseval N, Bénit L, Heidmann T: PNAS 2003, 100:13013-18. 4. Dupressoir A, Marceau G, Vernochet C, Benit L, Kanellopoulos C, Sapin V, Heidmann T: PNAS 2005, 102:725-30. from Frontiers of Retrovirology: Complex retroviruses, retroelements and their hosts Montpellier, France. 21-23 September 2009 Published: 24 September 2009 Retrovirology 2009, 6(Suppl 2):O3 doi:10.1186/1742-4690-6-S2-O3 <supplement> <title> <p>Frontiers of Retrovirology: Complex retroviruses, retroelements and their hosts</p> </title> <note>Meeting abstracts - A single PDF containing all abstracts in this Supplement is available <a href="http://www.biomedcentral.com/content/files/pdf/1742-4690-6-S2-full.pdf">here</a>.</note> <url>http://www.biomedcentral.com/content/pdf/1742-4690-6-S2-info.pdf</url> </supplement> This abstract is available from: http://www.retrovirology.com/content/6/S2/O3 © 2009 Dupressoir et al; licensee BioMed Central Ltd.

Transcript of The syncytin-A envelope gene of retroviral origin is essential for mouse placental development

Page 1: The syncytin-A envelope gene of retroviral origin is essential for mouse placental development

BioMed Central

Page 1 of 1(page number not for citation purposes)

Retrovirology

Open AccessOral presentationThe syncytin-A envelope gene of retroviral origin is essential for mouse placental developmentAnne Dupressoir*1, Cécile Vernochet1, Olivia Bawa2, Francis Harper3, Gérard Pierron3, Paule Opolon2 and Thierry Heidmann1

Address: 1Unité des Rétrovirus Endogènes et Eléments Rétroïdes des Eucaryotes Supérieurs, UMR 8122 CNRS, Institut Gustave Roussy, Villejuif, France, 2Vectorologie et Transfert de Gènes, UMR 8121, Institut Gustave Roussy, Villejuif, France and 3Laboratoire de Réplication de l'ADN et Ultrastructure du Noyau, FRE 2937 Institut André Lwoff, Villejuif, France

* Corresponding author

In several mammalian species, the fusion of throphoblas-tic cells into a multinucleated syncytiotrophoblast layer -taking place at the fetomaternal interface-constitutes a keyprocess of placenta morphogenesis. In the last years, twopairs of genes of retroviral origin encoding envelope pro-teins were identified in the human (syncytin-1 and -2) [1-3] and mouse (syncytin-A and -B) [4] genomes. Thesegenes, that were independently acquired through ancientretroviral infections of the primate and muridae lineage,20 to 40 MYA ago, display the characteristics of potentialeffectors of the trophoblast fusion process. In fact, syncy-tin genes are specifically expressed in the placenta, at theinterhaemal syncytial barrier, display cell-cell fusogenicactivity, and have been functionally conserved in evolu-tion.

Here, to definitely assess the role of these genes, we gener-ated knockout mice for syncytin-A. We show thathomozygous syncytin-A null embryos die in utero between11.5 and 13.5 days of gestation. Syncytin-A-deficient pla-centae exhibit disruption of the architecture of the syncy-tiotrophoblast-containing labyrinth, with overexpansionof trophoblast cells at the expense of fetal blood vesselsspaces, and defects in formation of one of the two interhe-mal syncytial layers. These results demonstrate that syncy-tin-A is essential for placenta development andsyncytiotrophoblast morphogenesis, and provide evi-dence that genes captured from ancestral retroviruses have

been pivotal in the acquisition of new important func-tions during mammalian evolution.

References1. Mi S, Lee X, Li X, Veldman G, Finnerty H, Racie L, LaVallie E, Tang X,

Edouard P, Howes S, Keith JJ, McCoy J: Nature 2000, 17:785-89.2. Blond JL, Lavillette D, Cheynet V, Bouton O, Oriol G, Chapel-Fern-

andes S, Mandrand B, Mallet F, Cosset FL: J Virol 2000, 74:3321-29.3. Blaise S, de Parseval N, Bénit L, Heidmann T: PNAS 2003,

100:13013-18.4. Dupressoir A, Marceau G, Vernochet C, Benit L, Kanellopoulos C,

Sapin V, Heidmann T: PNAS 2005, 102:725-30.

from Frontiers of Retrovirology: Complex retroviruses, retroelements and their hostsMontpellier, France. 21-23 September 2009

Published: 24 September 2009

Retrovirology 2009, 6(Suppl 2):O3 doi:10.1186/1742-4690-6-S2-O3

<supplement> <title> <p>Frontiers of Retrovirology: Complex retroviruses, retroelements and their hosts</p> </title> <note>Meeting abstracts - A single PDF containing all abstracts in this Supplement is available <a href="http://www.biomedcentral.com/content/files/pdf/1742-4690-6-S2-full.pdf">here</a>.</note> <url>http://www.biomedcentral.com/content/pdf/1742-4690-6-S2-info.pdf</url> </supplement>

This abstract is available from: http://www.retrovirology.com/content/6/S2/O3

© 2009 Dupressoir et al; licensee BioMed Central Ltd.