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Molecular and Cellular Biology, October 2006, p. 7760-7771, Vol. 26, No. 20
0270-7306/06/$08.00+0     doi:10.1128/MCB.00913-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Mutation in the Trap{alpha}/Ssr1 Gene, Encoding Translocon-Associated Protein {alpha}, Results in Outflow Tract Morphogenetic Defects{ddagger}

K. Mesbah,1,{dagger} A. Camus,2 C. Babinet,1 and J. Barra1*

Unité de Biologie du Développement, CNRS URA 2578, Institut Pasteur, 25 rue du Dr Roux, 75724 Paris Cedex 15, France,1 Laboratoire de Développement des Vertébrés, Institut Jacques Monod, CNRS UMR 7592, Universités Paris 6 et 7, 2 place Jussieu, 75251 Paris, France2

Received 23 May 2006/ Accepted 11 July 2006

Translocon-associated protein complex (TRAP) is thought to be required for efficient protein-specific translocation across the endoplasmic reticulum membrane. We created a mutation in the Trap{alpha} gene that leads to the synthesis of a truncated TRAP{alpha} protein fused to ShBle-ß-galactosidase. Analysis of Trap{alpha} cDNAs reveals that among three different messenger RNAs expressed in the mouse, one of them encodes a slightly larger protein that differs in its C-terminal end. This mRNA, specific for skeletal muscle and heart, is only expressed after birth. Homozygous Trap{alpha} mutant pups die at birth, likely as a result of severe cardiac defects. Indeed, the septation of the proximal part of the outflow tract is absent, resulting in a double-outlet right ventricle. Studies of protein secretion in transfected embryonic fibroblasts reveal that the TRAP complex does not function properly in homozygous mutant cells and confirm, in vivo, the involvement of TRAP in substrate-specific translocation. Our results provide the first in vivo demonstration that a member of the TRAP complex plays a crucial role in mammalian heart development and suggest that TRAP{alpha} could be involved in translocation of factors necessary for maturation of endocardial cushions.

* Corresponding author. Present address: Laboratoire EGDM, CNRS URA 2578, Institut Pasteur, 25 rue du Dr Roux, 75724 Paris Cedex 15, France. Phone: 33 1 45 68 85 61. Fax: 33 1 40 61 30 33. E-mail: barraja{at}pasteur.fr.

{ddagger} Supplemental material for this article may be found at http://mcb.asm.org/.

{dagger} Present address: IBDML, Campus de Lumigny, 13288 Marseille Cedex 9, France.

Molecular and Cellular Biology, October 2006, p. 7760-7771, Vol. 26, No. 20
0270-7306/06/$08.00+0     doi:10.1128/MCB.00913-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Obler, D, Juraszek, A L, Smoot, L B, Natowicz, M R (2008). Double outlet right ventricle: aetiologies and associations. J. Med. Genet. 45: 481-497 [Abstract] [Full Text]  
  • Hegde, R. S., Kang, S.-W. (2008). The concept of translocational regulation. JCB 182: 225-232 [Abstract] [Full Text]  


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