title: Ectodysplasin-A1 is sufficient to rescue both hair growth and sweat glands in Tabby mice.
abstract: Mutations in the human ectodysplasin-A (EDA) are responsible for the most common form of the ectodermal dysplasia and the defective orthologous gene in mice produces the tabby phenotype, suggesting its vital role in the development of hair, sweat glands and teeth. Among several EDA splice isoforms, the most common and the longest EDA splice isoforms, EDA-A1 and EDA-A2, differing by only two amino acids, activate NF-kappaB-promoted transcription by binding to distinct receptors, EDAR and XEDAR. The extent to which any particular isoform is sufficient for the formation of hair, sweat glands or teeth has remained unclear. Here we report that transgenic expression of the mouse EDA-A1 isoform in tabby (EDA-less) males rescued development of several skin appendages. The transgenic tabby mice showed almost complete restoration of hair growth, dermal ridges, sweat glands and molars. The number of hair follicles in the transgenic mice is the same as in wild-type; though the development of follicles and associated glands varies from indistinguishable from wild-type to smaller and/or only partially formed. These results suggest that the other EDA isoforms may not be absolutely required for skin appendage formation, but consistent with distinctive temporal and spatial expression of the EDA-A2 isoform, are likely required for appropriate timing and completeness of development. Our data provide the first direct physiological evidence that EDA-A1 is a key regulator of hair follicle and sweat gland initiation; its soluble ligand form could aid in deriving therapeutic reagents for conditions affecting hair and sweat gland formation.
authors.affiliation: J. C. Self Research Institute of Human Genetics, Greenwood Genetic Center, Greenwood, SC 29646, USA. anand@ggc.org
authors.forename: A K
authors.initials: AK
authors.lastname: Srivastava
authors.forename: M C
authors.initials: MC
authors.lastname: Durmowicz
authors.forename: A J
authors.initials: AJ
authors.lastname: Hartung
authors.forename: J
authors.initials: J
authors.lastname: Hudson
authors.forename: L V
authors.initials: LV
authors.lastname: Ouzts
authors.forename: D M
authors.initials: DM
authors.lastname: Donovan
authors.forename: C Y
authors.initials: CY
authors.lastname: Cui
authors.forename: D
authors.initials: D
authors.lastname: Schlessinger
mesh_terms: D000818:Animals; D053331:Ectodysplasins; D005260:Female; D006197:Hair / Q000254:growth & development* / Q000502:physiology; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D017434:Protein Structure, Tertiary; D012868:Skin Abnormalities; D013545:Sweat Glands / Q000254:growth & development / Q000502:physiology*; D013623:Tail; D014070:Tooth / Q000254:growth & development; D014071:Tooth Abnormalities
chemical_list: C506018:EDA protein, human; D053331:Ectodysplasins; C506019:Eda protein, mouse; D008565:Membrane Proteins