Inducible mEDA-A1 transgene mediates sebaceous gland hyperplasia and differential formation of two types of mouse hair follicles.
EDA splice isoforms EDA-A1 and EDA-A2 belong to the TNF ligand family and regulate skin appendage formation by activating NF-kappa B- and JNK- promoted transcription. To analyze their action further, we conditionally expressed the isoforms as tetracycline ('Tet')-regulated transgenes in Tabby (EDA-negative) and wild-type mice. Expression of only the mEDA-A1 transgene had two types of effects during embryogenesis: (1) determinative effects on sweat glands and hair follicles. In Tabby mice, one type of hair follicle ('guard hair') was restored, whereas a second type, the dominant undercoat hair follicle ('zigzag') was not; furthermore, the transgene sharply suppressed zigzag hair formation in wild-type mice, with the overall numbers of back hair follicles remaining the same; and (2) trophic effects on sebaceous and Meibomian glands. Marked hyperplasia resulted from expansion of the sebocyte-producing zone in sebaceous glands, with particularly high expression of the transgene and the replication marker PCNA, and correspondingly high production of sebum. The phenotypic effects of mEDA-A1 on sebaceous glands, but not on hair follicles, were reversed when the gene was repressed in adult animals. The results thus reveal both initiating and trophic isoform-specific effects of the EDA gene, and suggest a possible balance of isoform interactions in skin appendage formation.
Pubmed ID: 14506134 RIS Download
Animals | Cell Differentiation | Cell Division | Ectodysplasins | Enzyme Activation | Gene Expression Regulation | Hair Follicle | Hyperplasia | JNK Mitogen-Activated Protein Kinases | Membrane Proteins | Mice | Mice, Mutant Strains | Mice, Transgenic | Mitogen-Activated Protein Kinases | Models, Biological | NF-kappa B | Proliferating Cell Nuclear Antigen | Protein Isoforms | Protein Synthesis Inhibitors | RNA, Messenger | Sebaceous Glands | Sebum | Tetracycline | Transcription, Genetic | Transgenes