TY - JOUR
T1 - A new allele of the mouse hairless gene interferes with Hox/LacZ transgene regulation in hair follicle primordia
AU - Brancaz, Maud Virginie
AU - Iratni, Rabah
AU - Morrison, Alastair
AU - Mancini, Stéphane J.C.
AU - Marche, Patrice
AU - Sundberg, John
AU - Nonchev, Stefan
N1 - Funding Information:
We are very grateful to M. Lainé for animal husbandry and to A. Christiano for initial guidance in the mapping effort. We thank S. Khochbin, M. Maconochie, and A. Godwin for stimulating discussion. We appreciate the help and encouragement of R. Krumlauf and J.-J. Lawrence. This work was generously funded by La Fondation de la Recherche Médicale (S.N.), La Région Rhône-Alpes (M.-V.B.), and the National Institutes of Health (RR00173, CA34196, J.P.S.).
PY - 2004/4
Y1 - 2004/4
N2 - A new autosomal recessive mouse mutation, causing loss of hair in homozygous mice 2-3 weeks after birth, arose spontaneously in a colony at the National Institute for Medical Research (NIMR), Mill Hill, London in early 1998. Complementation analysis confirmed that this mutation was an allele of the hairless gene (hr). The gene symbol hrrhbm (hairless-rhino-bald Mill Hill) was assigned to reflect the source of the colony. Here we show the molecular defect in these mutants, which is a substantial deletion at the 3′-end of the hairless gene. Morphological and immunological analysis of the new hairless mutation was performed at early postnatal stages. In an effort to address the molecular and cellular mechanisms of the hairless phenotype, we analysed developmental stages before the establishment of alopecia. Using a HoxLacZ reporter line of transgenic mice, epidermal placode formation was followed in embryos. Homozygous mutant embryos (hrrhbmh/hr rhbmh), containing the LacZ reporter under the control of a Hoxb4 gene enhancer, display sharp loss of LacZ staining in epidermal cells invaginating to form the embryonic hair follicle placode. In the light of targeted mutagenesis data involving a Hox gene in the hair development [Genes Dev. 12 (1) (1998) 11], we discuss the potential implication of the hr rhbmh locus in cascades of Hox gene regulation during embryogenesis.
AB - A new autosomal recessive mouse mutation, causing loss of hair in homozygous mice 2-3 weeks after birth, arose spontaneously in a colony at the National Institute for Medical Research (NIMR), Mill Hill, London in early 1998. Complementation analysis confirmed that this mutation was an allele of the hairless gene (hr). The gene symbol hrrhbm (hairless-rhino-bald Mill Hill) was assigned to reflect the source of the colony. Here we show the molecular defect in these mutants, which is a substantial deletion at the 3′-end of the hairless gene. Morphological and immunological analysis of the new hairless mutation was performed at early postnatal stages. In an effort to address the molecular and cellular mechanisms of the hairless phenotype, we analysed developmental stages before the establishment of alopecia. Using a HoxLacZ reporter line of transgenic mice, epidermal placode formation was followed in embryos. Homozygous mutant embryos (hrrhbmh/hr rhbmh), containing the LacZ reporter under the control of a Hoxb4 gene enhancer, display sharp loss of LacZ staining in epidermal cells invaginating to form the embryonic hair follicle placode. In the light of targeted mutagenesis data involving a Hox gene in the hair development [Genes Dev. 12 (1) (1998) 11], we discuss the potential implication of the hr rhbmh locus in cascades of Hox gene regulation during embryogenesis.
KW - Embryogenesis
KW - Epidermis
KW - Hair follicle
KW - Hairless gene
KW - Hairless mice
KW - Hox gene regulation
KW - Transgenic mice
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U2 - 10.1016/j.yexmp.2003.10.003
DO - 10.1016/j.yexmp.2003.10.003
M3 - Article
C2 - 15010296
AN - SCOPUS:1542358810
SN - 0014-4800
VL - 76
SP - 173
EP - 181
JO - Experimental and Molecular Pathology
JF - Experimental and Molecular Pathology
IS - 2
ER -