Permanent correction of an inherited ectodermal dysplasia with recombinant EDA.

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Serval ID
serval:BIB_DAB001E64D04
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Permanent correction of an inherited ectodermal dysplasia with recombinant EDA.
Journal
Nature Medicine
Author(s)
Gaide O., Schneider P.
ISSN
1078-8956 (Print)
ISSN-L
1078-8956
Publication state
Published
Issued date
2003
Volume
9
Number
5
Pages
614-618
Language
english
Abstract
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.
Keywords
Amino Acid Sequence, Animals, Ectodermal Dysplasia/drug therapy, Female, Membrane Proteins/therapeutic use, Mice, Molecular Sequence Data, Pregnancy, Recombinant Fusion Proteins/therapeutic use
Pubmed
Web of science
Open Access
Yes
Create date
19/01/2008 17:30
Last modification date
20/08/2019 15:59
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