The Apoptosis-Related Gene Differential Expression in the Cochlea of GJB2 Gene Conditional Knockout Mice / 听力学及言语疾病杂志

ABSTRACT

Objective To study the differential expression of apoptosis related genes in GJB2 gene conditional knockout mice (cCx26Pax2Cre ) cochlea membranous labyrinth ,and to explore the mechanism of GJB2 gene mutations causing deafness .Methods Two developmental stages of P10 and P18 were selected from the knock out mice and the wild type ones (BALB/C) .The total RNA was isolated from cochlear membranous labyrinth and PCR array was performed using mouse apoptosis PCR arrays .Results Compared with wild -type mice ,significant up or down -regulation in gene expression was detected in 16 genes in cCx26Pax2Cre ones at P10 .Of the 16 genes ,14 ones were down-regulated .Among the 14 genes ,9 ones can be classified as anti -apoptosis or pro -proliferation genes ,5 ones can be classified as pro -apoptosis or pro -inflammation genes .The other 2 genes expression was up-regula-ted ,and their main role was to promote apoptosis .Compared with time -matched controls ,significant up or down-regulation in gene expression was detected in 4 genes in cCx26Pax2Cre mice at P18 .Of the 4 genes ,3 ones expression was down-regulated ,were anti-apoptosis ones .The expression of the other one gene among the 4 ones was up-regulated ,which acted as pro -apoptosis genes .Bcl2l10 and Tnfrsf10b expression showed significant down or up -regulation at both stages . Compared with P10 , the expression of caspase - 8 was up - ragulated at P18 in cCx26Pax2Cre mice .Conclusion It is suggested that GJB2 mutation may up -regulate the expression of DR5 ,which can trigger the death receptor pathway to cause apoptosis in cCx 26Pax2Cre mice cochlea directly .At the same time , caspase-8 in death receptor pathway may activate the mitochondria pathway indirectly and amplify the apoptosis further in cCx26Pax2Cre mice cochlea .The final result of the above activated pathways is the wide range of cochlear cells apoptosis and the profound hearing loss in cCx 26Pax2Cre mice .