A new allele of the mouse hairless gene interferes with Hox/LacZ transgene regulation in hair follicle primordia.
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 hr(rhbm) (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 (hr(rhbmh)/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, we discuss the potential implication of the hr(rhbmh) locus in cascades of Hox gene regulation during embryogenesis.
Brancaz
Maud-Virginie
MV
Institute Albert Bonniot, INSERM U309, La Tronche 38706, France.
Iratni
Rabah
R
Morrison
Alastair
A
Mancini
Stéphane J C
SJ
Marche
Patrice
P
Sundberg
John
J
Nonchev
Stefan
S
D000483:Alleles; D000818:Animals; D002454:Cell Differentiation; D004622:Embryo, Mammalian; D005434:Flow Cytometry; D018507:Gene Expression Regulation, Developmental; D017930:Genes, Reporter; D018859:Hair Follicle / Q000002:abnormalities*; D018398:Homeodomain Proteins / Q000235:genetics*; D017403:In Situ Hybridization; D007763:Lac Operon; D051379:Mice; D008812:Mice, Hairless / Q000235:genetics*; D008822:Mice, Transgenic; D016133:Polymerase Chain Reaction; D017384:Sequence Deletion; D013601:T-Lymphocytes / Q000166:cytology; D014157:Transcription Factors / Q000235:genetics*
D018398:Homeodomain Proteins; C513262:Hoxb4 protein, mouse; D014157:Transcription Factors