¹Institut Albert Bonniot, INSERM U823, University Joseph Fourier, La Tronche, France

Correspondence: Professor Stefan Nonchev, Institut Albert Bonniot, INSERM U823, Domaine de la Merci, 38706 La Tronche, France. E-mail: snonchev@ujf-grenoble.fr

²Current address: ERYtech, Pharma, 60 avenue Rockefeller, Lyon 69008, France.

³These authors have contributed equally to this work.

⁴Current address: Department of Genetic Medicine and Development CMU, Geneva, Switzerland.

⁵Co-senior authors.

Received 13 September 2006; Revised 10 May 2007; Accepted 24 May 2007; Published online 26 July 2007.

Abstract

We have previously identified a mutation in the mouse hairless locus—hairless rhino bald Mill Hill (Hr^rhbmh). The genetic alteration in these mice consists in a large 296 bp deletion at the 3' part of the hairless gene (ID:MGI:3039558; J:89321). Here, we show that this deletion removes the stop codon and creates a new reading frame at the C terminus of the hairless protein, generating a larger mutant protein harboring an additional sequence of 117 amino acids. The mutant hairless gene mRNA is expressed during the embryonic and post-natal development of the hair follicle. The mutant protein is identified in bmh mouse skin at different stages of development by a specific antibody. We demonstrate that the HR bmh protein is able to interact with the vitamin D receptor (VDR), but is not able to repress VDR-mediated transactivation. Immunofluorescence analysis reveals that HR bmh protein displays an abnormal cellular localization in transfected cell lines, as well as in the epidermis and hair follicle of bmh mutant mice. We discuss the relevance of the hairless protein mis localization in cell signalling pathways and with respect to the specific skin phenotype of mouse hairless mutants.