Dominant negative connexin26 mutation R75W causing severe hearing loss influences normal programmed cell death in postnatal organ of Corti.
Dominant negative connexin26 mutation R75W causing severe hearing loss influences normal programmed cell death in postnatal organ of Corti.
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DOI：
10.1186/1471-2156-15-1
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发表时间：
2014-01-03
期刊：
影响因子：
2.9
通讯作者：
Kamiya K
中科院分区：
文献类型：
--
作者：
Inoshita A;Karasawa K;Funakubo M;Miwa A;Ikeda K;Kamiya K
大上皮嵴（GER）是Corti器官成熟过程中的一个发育结构。位于新生小鼠内毛细胞附近的GER在出生后第8天发生凋亡（P8）。我们在携带R75W +突变的转基因小鼠中评估了从P8到P12的GER， R75W +突变是人类间隙连接蛋白β 2,26 kDa (GJB2)（也称为连接蛋白26或CX26）的显性阴性突变。Cx26促进哺乳动物听觉器官内的细胞间交流。在非转基因（非tg）和R75W +小鼠中，一些GER细胞在P8时表现出凋亡特征。在非tg小鼠的GER中，细胞总数和凋亡细胞数量从P8减少到P12。相比之下，R75W +小鼠在P12时的GER中仍明显可见凋亡细胞。因此，在R75W +小鼠中，GER中的细胞凋亡一直持续到耳蜗发育的后期。此外，R75W +小鼠的GER表现出保留的形态学迹象，这可能是由于胚胎发生和出生后早期发育阶段细胞凋亡水平降低和/或细胞增殖促进所致。本研究表明，Cx26功能障碍与GER细胞的延迟凋亡和GER保留有关。这是首次证实Cx26可能调节耳蜗发育过程中的细胞增殖和凋亡。
The greater epithelial ridge (GER) is a developmental structure in the maturation of the organ of Corti. Situated near the inner hair cells of neonatal mice, the GER undergoes a wave of apoptosis after postnatal day 8 (P8). We evaluated the GER from P8 to P12 in transgenic mice that carry the R75W + mutation, a dominant-negative mutation of human gap junction protein, beta 2, 26 kDa (GJB2) (also known as connexin 26 or CX26). Cx26 facilitate intercellular communication within the mammalian auditory organ. In both non-transgenic (non-Tg) and R75W + mice, some GER cells exhibited apoptotic characteristics at P8. In the GER of non-Tg mice, both the total number of cells and the number of apoptotic cells decreased from P8 to P12. In contrast, apoptotic cells were still clearly evident in the GER of R75W + mice at P12. In R75W + mice, therefore, apoptosis in the GER persisted until a later stage of cochlear development. In addition, the GER of R75W + mice exhibited morphological signs of retention, which may have resulted from diminished levels of apoptosis and/or promotion of cell proliferation during embryogenesis and early postnatal stages of development. Here we demonstrate that Cx26 dysfunction is associated with delayed apoptosis of GER cells and GER retention. This is the first demonstration that Cx26 may regulate cell proliferation and apoptosis during development of the cochlea.
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影响因子：
4.7
作者：
Tan, LW;Bianco, T;Dobrovic, A
通讯作者：
Dobrovic, A
影响因子：
3.3
作者：
Inoshita, A.;Iizuka, T.;Ikeda, K.
通讯作者：
Ikeda, K.
DOI：
10.1007/bf00305923
发表时间：
1983-01-01
期刊：
ANATOMY AND EMBRYOLOGY
影响因子：
--
作者：
ANNIKO, M
通讯作者：
ANNIKO, M
影响因子：
3.7
作者：
Hellmann, P;Grümmer, R;Winterhager, E
通讯作者：
Winterhager, E
影响因子：
64.8
作者：
Elias, Laura A. B.;Wang, Doris D.;Kriegstein, Arnold R.
通讯作者：
Kriegstein, Arnold R.