Abstract
Mutations in ectodysplasin-A (EDA) cause loss of hair, sweat glands, and teeth in man and mouse. Isoform EDA-A1 protein shows partial rescue of the affected Tabby mouse phenotypes, suggesting that other isoforms may be required for full function. We describe genomic structure for five EDA isoforms, EDA-A1', A5, A5', A6, and A6', in addition to the previously known EDA-A1, A2, A3, and A4. The novel isoforms together account for approximately 12% of total EDA transcripts. The most different, EDA-A6 and A6', which lack the critical domain for interaction with NF-kappaB-activating receptors, were nevertheless confirmed to be present in mouse and human skin tissue. Other isoforms, EDA-A5 and A5', for example, activated NF-kappaB through receptors EDAR and XEDAR. These properties make new isoforms candidates for modulators of EDA function.
Publication types
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Research Support, N.I.H., Intramural
MeSH terms
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Animals
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Cells, Cultured
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Ectodysplasins
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Edar Receptor
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Humans
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Keratinocytes / cytology
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Keratinocytes / metabolism*
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Membrane Proteins / genetics
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Membrane Proteins / metabolism*
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Mice
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NF-kappa B / metabolism
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Organ Specificity / physiology
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Protein Isoforms / genetics
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Protein Isoforms / metabolism
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Protein Structure, Tertiary / genetics
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Receptors, Ectodysplasin
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Receptors, Tumor Necrosis Factor / genetics
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Receptors, Tumor Necrosis Factor / metabolism
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Signal Transduction / physiology*
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Skin / cytology
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Skin / metabolism
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Tumor Necrosis Factors / genetics
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Tumor Necrosis Factors / metabolism*
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Xedar Receptor
Substances
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EDA protein, human
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EDA2R protein, human
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EDAR protein, human
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Ectodysplasins
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Eda protein, mouse
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Eda2r Protein, mouse
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Edar Receptor
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Edar protein, mouse
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Membrane Proteins
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NF-kappa B
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Protein Isoforms
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Receptors, Ectodysplasin
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Receptors, Tumor Necrosis Factor
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Tumor Necrosis Factors
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Xedar Receptor