This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Newton, K. Articles by Dixit, V. M. Search for Related Content PubMed PubMed Citation Articles by Newton, K. Articles by Dixit, V. M.

Myodegeneration in EDA-A2 Transgenic Mice Is Prevented by XEDAR Deficiency

Molecular Oncology Department,¹ Pathology Department, Genentech, Inc., South San Francisco, California²

Received 10 September 2003/ Returned for modification 24 October 2003/ Accepted 5 November 2003

EDA-A1 and EDA-A2 are members of the tumor necrosis factor family of ligands. The products of alternative splicing of the ectodysplasin (EDA) gene, EDA-A1 and EDA-A2 differ by an insertion of two amino acids and bind to distinct receptors. The longer isoform, EDA-A1, binds to EDAR and plays an important role in sweat gland, hair, and tooth development; mutations in EDA, EDAR, or the downstream adaptor EDARADD cause hypohidrotic ectodermal dysplasia. EDA-A2 engages the receptor XEDAR, but its role in the whole organism is less clear. We have generated XEDAR-deficient mice by gene targeting and transgenic mice expressing secreted forms of EDA-A1 or EDA-A2 downstream of the skeletal muscle-specific myosin light-chain 2 or skin-specific keratin 5 promoter. Mice lacking XEDAR were indistinguishable from their wild-type littermates, but EDA-A2 transgenic mice exhibited multifocal myodegeneration. This phenotype was not observed in the absence of XEDAR. Skeletal muscle in EDA-A1 transgenic mice was unaffected, but their sebaceous glands were hypertrophied and hyperplastic, consistent with a role for EDA-A1 in the development of these structures. These data indicate that XEDAR-transduced signals are dispensable for development of ectoderm-derived organs but might play a role in skeletal muscle homeostasis.

This article has been cited by other articles:

• Pantalacci, S., Chaumot, A., Benoit, G., Sadier, A., Delsuc, F., Douzery, E. J. P., Laudet, V. (2008). Conserved Features and Evolutionary Shifts of the EDA Signaling Pathway Involved in Vertebrate Skin Appendage Development. Mol Biol Evol 25: 912-928 [Abstract] [Full Text]  
• Schmidt-Ullrich, R., Tobin, D. J., Lenhard, D., Schneider, P., Paus, R., Scheidereit, C. (2006). NF-{kappa}B transmits Eda A1/EdaR signalling to activate Shh and cyclin D1 expression, and controls post-initiation hair placode down growth. Development 133: 1045-1057 [Abstract] [Full Text]  
• Mustonen, T., Ilmonen, M., Pummila, M., Kangas, A. T., Laurikkala, J., Jaatinen, R., Pispa, J., Gaide, O., Schneider, P., Thesleff, I., Mikkola, M. L. (2004). Ectodysplasin A1 promotes placodal cell fate during early morphogenesis of ectodermal appendages. Development 131: 4907-4919 [Abstract] [Full Text]  
• Sinha, S. K., Chaudhary, P. M. (2004). Induction of Apoptosis by X-linked Ectodermal Dysplasia Receptor via a Caspase 8-dependent Mechanism. J. Biol. Chem. 279: 41873-41881 [Abstract] [Full Text]