Spontaneous hair cell regeneration in the mouse utricle following gentamicin ototoxicity.
Spontaneous hair cell regeneration in the mouse utricle following gentamicin ototoxicity.
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DOI：
10.1016/j.heares.2008.08.010
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发表时间：
2009-01
期刊：
影响因子：
2.8
通讯作者：
Raphael Y
中科院分区：
文献类型：
--
作者：
Kawamoto K;Izumikawa M;Beyer LA;Atkin GM;Raphael Y
大多数上皮组织在创伤性损伤后会更新和再生，然而内耳的感觉上皮这种修复能力减弱；耳蜗中不存在这种能力，前庭上皮也仅有有限的再生能力。几种哺乳动物（包括豚鼠、大鼠和龙猫）的前庭毛细胞再生程度已有描述，但小鼠的情况尚未可知。作为研究遗传性疾病的基本模式生物，小鼠可以使用多种遗传和分子工具进行研究。为了设计一个用于前庭毛细胞再生研究的小鼠模型，我们实验室开发了一种氨基糖苷诱导的完全清除毛细胞的方法，并将其应用于小鼠椭圆囊。通过扫描电子显微镜观察到椭圆囊毛细胞的缺失，并且在具有绿色荧光蛋白阳性毛细胞的转基因小鼠的椭圆囊中，荧光信号的缺失也证实了这一点。在损伤后的多个时间点（直至6个月）对再生能力进行了表征。通过扫描电子显微镜，我们观察到早在损伤后两周，在椭圆囊中就可以看到一些未成熟的毛细胞，呈现出表明再生的典型未成熟形态。随着时间推移，可以看到更多的未成熟毛细胞以及一些类似II型毛细胞表面形态的成熟细胞。到损伤后6个月，椭圆囊中出现了大量再生的毛细胞，然而，其数量和外观都不正常。BrdU检测表明，小鼠前庭毛细胞的再生至少在某些情况下涉及有丝分裂。我们的研究结果表明，小鼠的前庭感觉上皮能够自发再生，阐明了这一过程的时间进程，并确定了在某些情况下有丝分裂的参与。这些数据为小鼠前庭再生过程绘制了一幅路线图，可用于阐明控制这一过程的分子事件。
Whereas most epithelial tissues turn-over and regenerate after a traumatic lesion, this restorative ability is diminished in the sensory epithelia of the inner ear; it is absent in the cochlea and exists only in a limited capacity in the vestibular epithelium. The extent of regeneration in vestibular hair cells has been characterized for several mammalian species including guinea pig, rat, and chinchilla, but not yet in mouse. As the fundamental model species for investigating hereditary disease, the mouse can be studied using a wide variety of genetic and molecular tools. To design a mouse model for vestibular hair cell regeneration research, an aminoglycoside-induced method of complete hair cell elimination was developed in our lab and applied to the murine utricle. Loss of utricular hair cells was observed using scanning electron microscopy, and corroborated by a loss of fluorescent signal in utricles from transgenic mice with GFP-positive hair cells. Regenerative capability was characterized at several time points up to six months following insult. Using scanning electron microscopy, we observed that as early as two weeks after insult, a few immature hair cells, demonstrating the characteristic immature morphology indicative of regeneration, could be seen in the utricle. As time progressed, larger numbers of immature hair cells could be seen along with some mature cells resembling surface morphology of type II hair cells. By six months post-lesion, numerous regenerated hair cells were present in the utricle, however, neither their number nor their appearance was normal. A BrdU assay suggested that at least some of the regeneration of mouse vestibular hair cells involved mitosis. Our results demonstrate that the vestibular sensory epithelium in mice can spontaneously regenerate, elucidate the time course of this process, and identify involvement of mitosis in some cases. These data establish a road map of the murine vestibular regenerative process, which can be used for elucidating the molecular events that govern this process.
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DOI：
10.1073/pnas.101120898
发表时间：
2001-05-08
影响因子：
11.1
作者：
Kopke, RD;Jackson, RL;Van De Water, TR
通讯作者：
Van De Water, TR
影响因子：
3.4
作者：
López, I;Honrubia, V;Beykirch, K
通讯作者：
Beykirch, K
DOI：
10.1016/s0736-5748(96)00104-9
发表时间：
1997-07-01
影响因子：
1.8
作者：
Sobkowicz, HM;August, BK;Slapnick, SM
通讯作者：
Slapnick, SM
影响因子：
1.4
作者：
Sobkowicz, HM;August, BK;Slapnick, SM
通讯作者：
Slapnick, SM
影响因子：
56.9
作者：
FORGE, A;LI, L;NEVILL, G
通讯作者：
NEVILL, G