内耳间隙连接和连接蛋白基因家族与遗传性聋

耳蜗有非感觉上皮细胞和结缔组织细胞2套间隙连接系统,内耳前庭的感觉上皮也有间隙连接。已发现在内耳表达的连接蛋白有Cx26、Cx30、Cx31、Cx32、Cx43和Cx45。连接蛋白是同一基因家族编码,其中GJB2(Cx26)、GJB3(Cx31)、GJB6(Cx30)、GJA1(Cx43)、GJB1(Cx32)都与遗传性聋有关。GJB2基因敲除小鼠在胚胎期致死。GJB3敲除小鼠60%在胚胎死亡,成活小鼠无耳聋和皮肤疾病等表型。GJA1裸鼠表现心脏发育缺陷与膜内和软骨内成骨延迟。GJB1敲除小鼠表型无明显异常,但外周神经表现脱髓鞘改变。不同间隙连接的缺陷导致听力下降的机制可能不同。间隙连接与耳聋关系的深入研究,可能有助于阐明听觉和耳聋的部分机制。

Gap junction system in the inner ear and gap junctional protein gene family related to hereditary hearing loss

Objective There are two systems of gap junction in the cochlea, including the system of non-sensory epithelial cells and the system of connective-tissue cells. There are also gap junctions in the sensory epithelia of the vestibule of the inner ear. Connexin (Cx) 26, Cx30, Cx31, Cx32, Cx43 and Cx45 have been found to express in the inner ear. Connexins are translated by the gap junction protein genes that belong to one gene family. GJB2 (Cx26), GJB3 (Cx31), GJB6(Cx30), GJA1 (Cx43), and GJB1 (Cx32) are responsible for hereditary hearing loss. GJB2 gene knockout mice led to death during embryonic period. 60% embryo mice with GJB3 absence were dead and the rest had no abnormal phenotype of hearing and skin after birth. GJA1 null mice resulted in heart malformations and delayed intramembranous and endochondral ossification. GJB1 knockout mice developed a progressive demyelinating peripheral neuropathy. The deafness-causing mechanisms by the defects of different Cx in the inner ear might be different. The study of the relationship between the gap junction and the hearing loss may help to elucidate partial mechanism of hearing and hearing impairment.