Inducible mEDA-A1 transgene mediates sebaceous gland hyperplasia and differential formation of two types of mouse hair follicles
Inducible mEDA-A1 transgene mediates sebaceous gland hyperplasia and differential formation of two types of mouse hair follicles
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DOI：
10.1093/hmg/ddg325
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发表时间：
2003-11-15
影响因子：
3.5
通讯作者：
Schlessinger, D
中科院分区：
文献类型：
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作者：
Cui, CY;Durmowicz, M;Schlessinger, D
EDA剪接亚型EDA-A1和EDA-A2属于TNF配体家族，并通过激活NF-κ B和JNK促进的转录来调节皮肤附件形成。为了进一步分析它们的作用，我们在Tabby（EDA阴性）和野生型小鼠中有条件地表达了作为四环素（'Tet'）调节的转基因的同种型。在胚胎发生过程中，仅mEDA-A1转基因的表达具有两种类型的作用：（1）对汗腺和毛囊的决定性作用。在虎斑小鼠中，一种类型的毛囊（“保卫毛”）得到恢复，而第二种类型，占主导地位的底毛毛囊（“之字形”）没有恢复;此外，转基因显著抑制了野生型小鼠中之字形毛的形成，背部毛囊的总数保持不变;（2）对皮脂腺和睑板腺的营养作用。皮脂腺中皮脂细胞生成区的扩张导致显著增生，转基因和复制标记物PCNA的表达特别高，相应地皮脂的产生也高。mEDA-A1对皮脂腺的表型效应，但不是对毛囊，逆转时，该基因在成年动物中被抑制。因此，结果揭示了EDA基因的启动和营养异构体特异性效应，并表明皮肤附件形成中异构体相互作用的可能平衡。
EDA splice isoforms EDA-A1 and EDA-A2 belong to the TNF ligand family and regulate skin appendage formation by activating NF-kB- 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.