title: Overexpression of Hr links excessive induction of Wnt signaling to Marie Unna hereditary hypotrichosis.
abstract: Marie Unna hereditary hypotrichosis (MUHH) is a rare autosomal dominant hair disorder. Through the study of a mouse model, we identified a mutation in the 5'-untranslated region of the hairless (HR) gene in patients with MUHH in a Caucasian family. The corresponding mutation, named 'hairpoor', was found in mutant mice that were generated through N-ethyl-N-nitrosourea mutagenesis. Hairpoor mouse mutants display partial hair loss at an early age and progress to near alopecia, which resembles the MUHH phenotype. This mutation conferred overexpression of HR through translational derepression and, in turn, decreased the expression of Sfrp2, an inhibitor of the Wnt signaling pathway. This study indicates that the gain in function of HR also results in alopecia, as seen with the loss of function of HR, via abnormal upregulation of the Wnt signaling pathway.
authors.affiliation: Department of Biomedical Sciences, The Catholic University of Korea, 505 Banpo-dong, Seocho-ku, Seoul, Korea.
authors.forename: Jeong-Ki
authors.initials: JK
authors.lastname: Kim
authors.forename: Eunmin
authors.initials: E
authors.lastname: Kim
authors.forename: In-Cheol
authors.initials: IC
authors.lastname: Baek
authors.forename: Bong-Kyu
authors.initials: BK
authors.lastname: Kim
authors.forename: A-Ri
authors.initials: AR
authors.lastname: Cho
authors.forename: Tae-Yoon
authors.initials: TY
authors.lastname: Kim
authors.forename: Chang-Woo
authors.initials: CW
authors.lastname: Song
authors.forename: Je Kyung
authors.initials: JK
authors.lastname: Seong
authors.forename: Jong-Bok
authors.initials: JB
authors.lastname: Yoon
authors.forename: Kurt S
authors.initials: KS
authors.lastname: Stenn
authors.forename: Satish
authors.initials: S
authors.lastname: Parimoo
authors.forename: Sungjoo Kim
authors.initials: SK
authors.lastname: Yoon
mesh_terms: D020121:5' Untranslated Regions; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D004195:Disease Models, Animal; D005260:Female; D015870:Gene Expression; D006801:Humans; D007039:Hypotrichosis / Q000151:congenital* / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D008812:Mice, Hairless; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D015854:Up-Regulation; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D020121:5' Untranslated Regions; C490267:HR protein, human; D014157:Transcription Factors; D051153:Wnt Proteins; C088661:hr protein, mouse