title: The activation level of the TNF family receptor, Edar, determines cusp number and tooth number during tooth development.
abstract: Mutations in members of the ectodysplasin (TNF-related) signalling pathway, EDA, EDAR, and EDARADD in mice and humans produce an ectodermal dysplasia phenotype that includes missing teeth and smaller teeth with reduced cusps. Using the keratin 14 promoter to target expression of an activated form of Edar in transgenic mice, we show that expression of this transgene is able to rescue the tooth phenotype in Tabby (Eda) and Sleek (Edar) mutant mice. High levels of expression of the transgene in wild-type mice result in molar teeth with extra cusps, and in some cases supernumerary teeth, the opposite of the mutant phenotype. The level of activation of Edar thus determines cusp number and tooth number during tooth development.
authors.affiliation: Craniofacial Development, Dental Institute, Guy's Hospital, King's College London, London SE1 9RT, UK.
authors.forename: A S
authors.initials: AS
authors.lastname: Tucker
authors.forename: D J
authors.initials: DJ
authors.lastname: Headon
authors.forename: J-M
authors.initials: JM
authors.lastname: Courtney
authors.forename: P
authors.initials: P
authors.lastname: Overbeek
authors.forename: P T
authors.initials: PT
authors.lastname: Sharpe
mesh_terms: D000818:Animals; D001483:Base Sequence; D017931:DNA Primers; D003743:Dental Enamel; D053339:Edar Receptor; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D053338:Receptors, Ectodysplasin; D018124:Receptors, Tumor Necrosis Factor; D014070:Tooth / Q000254:growth & development*
chemical_list: D017931:DNA Primers; C506008:EDAR protein, human; D053339:Edar Receptor; C506009:Edar protein, mouse; D008565:Membrane Proteins; D053338:Receptors, Ectodysplasin; D018124:Receptors, Tumor Necrosis Factor