TY - JOUR
T1 - The "bald Mill Hill" mutation in the mouse is associated with an abnormal, mislocalized HR bmh protein
AU - Brancaz-Bouvier, Maud Virginie
AU - Folco, Eric J.G.
AU - Salameire, Dimitri
AU - Romero, Yannick
AU - Iratni, Rabah
AU - Nonchev, Stefan
N1 - Funding Information:
We thank Dr Henry Gronmayer for supplying the VDR and RXR plasmid constructs, Dr Angela Nieto for the mouse and human keratinocyte cell lines, and Drs Daniel Bikle, Yuko Oda, and Leonard Freedman for the VDRE reporter plasmids. This work was supported by the “Emergence” grant of the Region Rhône—Alpes and by the French Fondation de la Recherche Médicale (S.N.). M.-V.B. and E.F. had a PhD fellowship of the French Ministry of National Education. We appreciate helpful discussion with Stefan Dimitrov and Saadi Khochbin. We are grateful to Martine Le Pipec for an excellent mice care and to Brigitte Peyrusse for skillful artwork. A special thanks goes to Drs John Sundberg and Robb Krumlauf for their generous encouragement and suggestions.
PY - 2008/2
Y1 - 2008/2
N2 - We have previously identified a mutation in the mouse hairless locus-hairless rhino bald Mill Hill (Hrrhbmh). 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.
AB - We have previously identified a mutation in the mouse hairless locus-hairless rhino bald Mill Hill (Hrrhbmh). 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.
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U2 - 10.1038/sj.jid.5700998
DO - 10.1038/sj.jid.5700998
M3 - Article
C2 - 17657241
AN - SCOPUS:38149061181
SN - 0022-202X
VL - 128
SP - 311
EP - 321
JO - Journal of Investigative Dermatology
JF - Journal of Investigative Dermatology
IS - 2
ER -