Molecular and Cellular Biology, February 2004, p. 1608-1613, Vol. 24, No. 4
0270-7306/04/$08.00+0 DOI: 10.1128/MCB.24.4.1608-1613.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.
Myodegeneration in EDA-A2 Transgenic Mice Is Prevented by XEDAR Deficiency
Kim Newton,1 Dorothy M. French,2 Minhong Yan,1 Gretchen D. Frantz,2 and Vishva M. Dixit1*
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.
* Corresponding author. Mailing address: Molecular Oncology, Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080. Phone: (650) 225-1312. Fax: (650) 225-6127. E-mail: dixit{at}gene.com.
Molecular and Cellular Biology, February 2004, p. 1608-1613, Vol. 24, No. 4
0022-538X/04/$08.00+0 DOI: 10.1128/MCB.24.4.1608-1613.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.
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Copyright © 2004 by the American Society for Microbiology. All rights reserved.