Overexpression of parathyroid hormone-related protein in the skin of transgenic mice interferes with hair follicle development.

Overexpression of parathyroid hormone-related protein in the skin of transgenic mice interferes with hair follicle development.
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DOI:
10.1073/pnas.91.3.1133
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发表时间:
1994-02
影响因子:
11.1
通讯作者:
J. Wysolmerski;A. Broadus;Jing Zhou;E. Fuchs;L. Milstone;W. Philbrick
J. Wysolmerski;A. Broadus;Jing Zhou;E. Fuchs;L. Milstone;W. Philbrick
中科院分区:
综合性期刊1区
文献类型:
--
作者:
J. Wysolmerski;A. Broadus;Jing Zhou;E. Fuchs;L. Milstone;W. Philbrick

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甲状旁腺素相关肽(PTHrP)最初被发现是恶性肿瘤体液性高钙血症综合征的病因。随后,PTHrP基因已被证明在各种正常组织中表达,包括皮肤。由于PTHrP在皮肤中的生物学功能仍然未知,我们使用人角蛋白14启动子将PTHrP的过表达靶向转基因小鼠的皮肤。我们在皮肤中实现了10倍的过表达水平,并且人角蛋白14启动子-PTHrP转基因小鼠在正常毛囊发育中显示出紊乱。这些小鼠要么未能启动卵泡发育,要么显示卵泡启动延迟。这些发现表明PTHrP通常在毛囊发育的早期阶段起作用,并支持先前的推测,即肽可能在调节细胞分化中起作用。
Parathyroid hormone-related peptide (PTHrP) was initially discovered as the cause of the syndrome of humoral hypercalcemia of malignancy. Subsequently, the PTHrP gene has been shown to be expressed in a wide variety of normal tissues, including skin. Because the biological function of PTHrP in skin remains unknown, we used the human keratin 14 promoter to target overexpression of PTHrP to the skin of transgenic mice. We achieved a 10-fold level of overexpression in skin, and human keratin 14 promoter-PTHrP transgenic mice displayed a disturbance in normal hair follicle development. These mice either failed to initiate follicle development or showed a delay in the initiation of follicles. These findings suggest that PTHrP normally plays a role in the early stages of hair follicle development and support previous speculation that the peptide may function in regulating cellular differentiation.