Abstract.
The ectodysplasin 1 gene (ED1) encodes a signaling molecule of the tumor necrosis factor family that is involved in fetal development of ectodermal appendages. Mutations in the ED1 gene are responsible for X-linked anhidrotic ectodermal dysplasia characterized by impaired development of hair, teeth, and eccrine sweat glands in human, mouse, and cattle. Two isoforms of ectodysplasin 1, termed ED1-A1 and ED1-A2, arise by alternative splicing and bind to different receptors. We identified a novel ED1 splice site mutation in a cattle family with X-linked anhidrotic ectodermal dysplasia. The point mutation is located within a 5′ splice site (splice donor) at the beginning of intron 8 that is used exclusively in the alternatively spliced ED1-A1 transcript. Remarkably, cDNA sequencing demonstrated that both physiological transcripts, i.e., the ED1-A1 and the ED1-A2 splice variant, were affected by this point mutation. In an affected animal, the use of cryptic internal splice donor and acceptor sites within exon 8 lead to the production of a single transcript lacking 51 or 45 bp with respect to the normal ED1-A1 or ED1-A2 transcripts, respectively. The translated protein of the mutated transcript contained a large deletion in the functionally important C-terminal tumor necrosis factor-like domain thus causing the observed phenotype of anhidrotic ectodermal dysplasia. Our findings suggest the presence of a splice enhancer in the ED1 gene in the region of the mutation.
Similar content being viewed by others
Author information
Authors and Affiliations
Additional information
Electronic Publication
Rights and permissions
About this article
Cite this article
Drögemüller, C., Peters, M., Pohlenz, J. et al. A single point mutation within the ED1 gene disrupts correct splicing at two different splice sites and leads to anhidrotic ectodermal dysplasia in cattle. J Mol Med 80, 319–323 (2002). https://doi.org/10.1007/s00109-002-0320-z
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00109-002-0320-z