Permanent correction of an inherited ectodermal dysplasia with recombinant EDA.
Data(s) |
2003
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Resumo |
X-linked hypohidrotic ectodermal dysplasia (XLHED; OMIM 305100) is a genetic disorder characterized by absence or deficient function of hair, teeth and sweat glands. Affected children may experience life-threatening high fever resulting from reduced ability to sweat. Mice with the Tabby phenotype share many symptoms with human XLHED patients because both phenotypes are caused by mutations of the syntenic ectodysplasin A gene (Eda) on the X chromosome. Two main splice variants of Eda, encoding EDA1 and EDA2, engage the tumor necrosis factor (TNF) family receptors EDAR and XEDAR, respectively. The EDA1 protein, acting through EDAR, is essential for proper formation of skin appendages; the functions of EDA2 and XEDAR are not known. EDA1 must be proteolytically processed to a soluble form to be active. Here, we show that treatment of pregnant Tabby mice with a recombinant form of EDA1, engineered to cross the placental barrier, permanently rescues the Tabby phenotype in the offspring. Notably, sweat glands can also be induced by EDA1 after birth. This is the first example of a developmental genetic defect that can be permanently corrected by short-term treatment with a recombinant protein. |
Identificador |
http://serval.unil.ch/?id=serval:BIB_DAB001E64D04 isbn:1078-8956 (Print) pmid:12692542 doi:10.1038/nm861 isiid:000182610600044 http://my.unil.ch/serval/document/BIB_DAB001E64D04.pdf http://nbn-resolving.org/urn/resolver.pl?urn=urn:nbn:ch:serval-BIB_DAB001E64D047 |
Idioma(s) |
en |
Direitos |
info:eu-repo/semantics/openAccess |
Fonte |
Nature Medicine, vol. 9, no. 5, pp. 614-618 |
Palavras-Chave | #Amino Acid Sequence; Animals; Ectodermal Dysplasia/drug therapy; Female; Membrane Proteins/therapeutic use; Mice; Molecular Sequence Data; Pregnancy; Recombinant Fusion Proteins/therapeutic use |
Tipo |
info:eu-repo/semantics/article article |