Human Molecular Genetics Advance Access first published online on November 6, 2009
This version [Corrected Proof] published online on November 23, 2009
Human Molecular Genetics, doi:10.1093/hmg/ddp509
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Overexpression of Hr links excessive induction of Wnt signaling to Marie Unna hereditary hypotrichosis
1 Research Institute of Molecular Genetics, 2 Department of Biomedical Sciences and 3 Department of Dermatology, College of Medicine, The Catholic University of Korea, Seoul 137-701, Korea, 4 Laboratory of Toxicogenomics, Korea Institute of Toxicology, Taejon 305-343, Korea, 5 Department of Veterinary Medical Science, The Seoul National University, Seoul 151-742, Korea, 6 Department of Biochemistry, Yonsei University, Seoul 120-749, Korea and 7 Aderans Research Institute, Philadelphia, PA 19104, USA
* To whom correspondence should be addressed at: Department of Biomedical Sciences, The Catholic University of Korea, 505 Banpo-dong, Seocho-ku, Seoul 137-701, Korea. Tel: +82 222587474; Fax: +82 25942385; Email: sjkyoon{at}catholic.ac.kr
Received August 6, 2009; Accepted November 4, 2009
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.