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RXR-alpha ablation in skin keratinocytes results in alopecia and epidermal alterations.
- Source :
-
Development (Cambridge, England) [Development] 2001 Mar; Vol. 128 (5), pp. 675-88. - Publication Year :
- 2001
-
Abstract
- RXR-alpha is the most abundant of the three retinoid X receptors (RXRs) in the epidermis. In this study, we have used Cre-mediated recombination to selectively disrupt the mouse gene for RXR-alpha in epidermal and hair follicle keratinocytes. We show that RXR-alpha is apparently dispensable for prenatal epidermal development, while it is involved in postnatal skin maturation. After the first hair pelage, mutant mice develop a progressive alopecia, histologically characterised by the destruction of hair follicle architecture and the formation of utriculi and dermal cysts in adult mice. Our results demonstrate that RXR-alpha plays a key role in anagen initiation during the hair follicle cycle. In addition, RXR-alpha ablation results in epidermal interfollicular hyperplasia with keratinocyte hyperproliferation and aberrant terminal differentiation, accompanied by an inflammatory reaction of the skin. Our data not only provide genetic evidence that RXR-alpha/VDR heterodimers play a major role in controlling hair cycling, but also suggest that additional signalling pathways mediated by RXR-alpha heterodimerised with other nuclear receptors are involved in postnatal hair follicle growth, and homeostasis of proliferation/differentiation of epidermal keratinocytes and of the skin's immune system.
- Subjects :
- Alopecia genetics
Alopecia pathology
Animals
Blotting, Southern
Cell Differentiation
Cloning, Molecular
Cysts pathology
DNA genetics
DNA metabolism
Epidermis growth & development
Epidermis immunology
Epidermis ultrastructure
Female
Genes, Reporter
Hair Follicle growth & development
Hair Follicle ultrastructure
Immunohistochemistry
Integrases genetics
Integrases metabolism
Intercellular Adhesion Molecule-1 metabolism
Keratinocytes metabolism
Male
Mice
Mice, Inbred Strains
Mice, Transgenic
Plasmids
Receptors, Retinoic Acid genetics
Recombination, Genetic
Retinoid X Receptors
T-Lymphocyte Subsets metabolism
Transcription Factors genetics
Transgenes
beta-Galactosidase metabolism
Epidermis anatomy & histology
Keratinocytes cytology
Keratins metabolism
Receptors, Retinoic Acid metabolism
Transcription Factors metabolism
Viral Proteins
Subjects
Details
- Language :
- English
- ISSN :
- 0950-1991
- Volume :
- 128
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Development (Cambridge, England)
- Publication Type :
- Academic Journal
- Accession number :
- 11171393
- Full Text :
- https://doi.org/10.1242/dev.128.5.675