Disrupted Ectodermal Organ Morphogenesis in Mice with a Conditional Histone Deacetylase 1, 2 Deletion in the Epidermis
Disrupted Ectodermal Organ Morphogenesis in Mice with a Conditional Histone Deacetylase 1, 2 Deletion in the Epidermis
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DOI：
10.1038/jid.2013.283
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发表时间：
2014-01-01
影响因子：
6.5
通讯作者：
Chuong, Cheng M.
中科院分区：
文献类型：
--
作者：
Hughes, Michael W.;Jiang, Ting-Xin;Chuong, Cheng M.
组蛋白脱乙酰酶（HDAC）存在于皮肤的表皮层、外根鞘和毛发基质中。为了研究组蛋白乙酰化如何影响皮肤形态发生和稳态，用K14启动子介导的Hdacl或Hdac 2减少产生小鼠。HDAC 1 null（K14-Cre Hdac 1（cKO/cKO））小鼠的皮肤表现出一系列病变，包括毛囊间表皮不规则增厚、脱发、毛囊营养不良、爪营养不良和异常色素沉着。毛稀疏、短、间断盘绕。独特的皮毛类型丢失。在第一个毛发周期中，毛发脱落并被具有扩张漏斗的营养不良毛囊所取代。营养不良的毛囊上皮是复层的，K14、外皮蛋白和TRP 63阳性，但角蛋白10阴性。一些营养不良的毛囊呈K15阳性，但成熟的毛纤维角蛋白缺失。脚趾在侧面形成额外的色素沉着的爪子。在滤泡间上皮、尾部和足中观察到色素沉着过度。Hdac 1和Hdac 2双转基因小鼠（K14-Cre Hdac 1（cKO/cKO）Hdac 2（+/cKO））具有相似但更明显的异常。这些结果表明，抑制表皮HDAC活性导致不适当的外胚层器官形态发生和破坏毛囊再生和稳态，以及对色素沉着的间接影响。
Histone deacetylases (HDACs) are present in the epidermal layer of the skin, outer root sheath, and hair matrix. To investigate how histone acetylation affects skin morphogenesis and homeostasis, mice were generated with a K14 promoter-mediated reduction of Hdacl or Hdac2. The skin of HDAC1 null (K14-Cre Hdac1(cKO/cKO)) mice exhibited a spectrum of lesions, including irregularly thickened interfollicular epidermis, alopecia, hair follicle dystrophy, claw dystrophy, and abnormal pigmentation. Hairs are sparse, short, and intermittently coiled. The distinct pelage hair types are lost. During the first hair cycle, hairs are lost and replaced by dystrophic hair follicles with dilated infundibulae. The dystrophic hair follicle epithelium is stratified and is positive for K14, involucrin, and TRP63, but negative for keratin 10. Some dystrophic follicles are K15 positive, but mature hair fiber keratins are absent. The digits form extra hyperpigmented claws on the lateral sides. Hyperpigmentation is observed in the interfollicular epithelium, the tail, and the feet. Hdacl and Hdac2 dual transgenic mice (K14-Cre Hdac1(cKO/cKO) Hdac2(+/cKO)) have similar but more obvious abnormalities. These results show that suppression of epidermal HDAC activity leads to improper ectodermal organ morphogenesis and disrupted hair follicle regeneration and homeostasis, as well as indirect effects on pigmentation.