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.
D000818:Animals; D002454:Cell Differentiation; D002455:Cell Division; D053331:Ectodysplasins; D004789:Enzyme Activation; D005786:Gene Expression Regulation; D018859:Hair Follicle / Q000254:growth & development*; D006965:Hyperplasia / Q000235:genetics*; D048031:JNK Mitogen-Activated Protein Kinases; D008565:Membrane Proteins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D008954:Models, Biological; D016328:NF-kappa B / Q000378:metabolism; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012627:Sebaceous Glands / Q000254:growth & development* / Q000473:pathology; D012629:Sebum / Q000378:metabolism; D013752:Tetracycline / Q000494:pharmacology; D014158:Transcription, Genetic; D019076:Transgenes
D053331:Ectodysplasins; C506019:Eda protein, mouse; D008565:Membrane Proteins; D016328:NF-kappa B; D018809:Proliferating Cell Nuclear Antigen; D020033:Protein Isoforms; D011500:Protein Synthesis Inhibitors; D012333:RNA, Messenger; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D013752:Tetracycline