Spag6 Mutant Mice Have Defects in Development and Function of Spiral Ganglion Neurons, Apoptosis, and Higher Sensitivity to Paclitaxel.
Spag6 Mutant Mice Have Defects in Development and Function of Spiral Ganglion Neurons, Apoptosis, and Higher Sensitivity to Paclitaxel.
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Spag6突变小鼠螺旋神经节神经元发育和功能缺陷、细胞凋亡以及对紫杉醇的敏感性更高
DOI：
10.1038/s41598-017-08739-8
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发表时间：
2017-08-17
影响因子：
4.6
通讯作者：
Wang H
中科院分区：
文献类型：
--
作者：
Li X;Xu L;Sun G;Wu X;Bai X;Li J;Strauss JF;Zhang Z;Wang H
哺乳动物精子相关抗原6（Mammalian Sperm Associated Antigen 6，SPAG 6）是衣原体PF 16的直向同源物，衣原体PF 16是一种定位于轴丝中央器的蛋白质。最近的研究表明Spag 6在脑神经元的增殖和分化中起作用。哺乳动物的螺旋神经节神经元（SGN）是内耳中的特化双极神经元。然而，SPAG 6在SGN中的作用尚未阐明。因此，我们假设Spag 6基因敲除会影响SGN的发育和功能。我们利用Spag 6缺陷小鼠和SGN外植体来定义SPAG 6的作用。出生后第30天（P30），与野生型同窝小鼠相比，突变小鼠的SGN密度较低，并且突变体中细胞凋亡更多。Bax表达增加，细胞色素c分布紊乱，以及裂解的caspase-3阳性染色表明凋亡增加涉及线粒体途径。透射电子显微镜显示异常的超微结构的突变SGNs早在P7。在体外，SPAG 6的缺乏影响神经突起和生长锥的生长。此外，SPAG 6缺陷降低了SGN外植体中的突触密度。最后，Spag 6突变SGN对微管稳定剂紫杉醇更敏感。这些发现表明Spag 6在SGN的发育和功能中起着至关重要的作用。
Mammalian Sperm Associated Antigen 6 (SPAG6) is the orthologue of Chlamydomonas PF16, a protein localized in the axoneme central apparatus. Recent studies showed that Spag6 has a role in brain neuronal proliferation and differentiation. The mammalian spiral ganglion neurons (SGNs) are specialzed bipolar neurons in the inner ear. However, the role of SPAG6 in SGN has not been elucidated. Therefore, We hypothesized that a Spag6 knockout would affect the development and function of SGNs. We utilized Spag6-deficient mice and SGN explants to define the role of SPAG6. On postnatal day 30 (P30) mutant mice had lower SGN density compared to their wild-type littermates, and more apoptosis was evident in the mutants. Increased Bax expression, a disturbed distribution of cytochrome c, and cleaved caspase-3 positive staining indicated that increased apoptosis involved a mitochondrial pathway. Transmission electron microscopy revealed abnormalities in the ultrastructure of mutant SGNs as early as P7. In vitro, lack of SPAG6 affected the growth of neurites and growth cones. Additionally, SPAG6 deficiency decreased synapse density in SGN explants. Finally, Spag6 mutant SGNs were more sensitive to the microtubule stabilizing agent, paclitaxel. These findings suggest that Spag6 plays a crucial role in SGN development and function.
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影响因子：
5.3
作者：
Bouquet, C;Soares, S;Nothias, F
通讯作者：
Nothias, F
影响因子：
3.5
作者：
Rizzo, Federica;Ronchi, Dario;Corti, Stefania
通讯作者：
Corti, Stefania
影响因子：
11.5
作者：
Steinbach, Daniel;Bader, Peter;Gruhn, Bernd
通讯作者：
Gruhn, Bernd
影响因子：
3.3
作者：
Schmitt, U.;Tanimoto, N.;Leube, R. E.
通讯作者：
Leube, R. E.
影响因子：
4.7
作者：
Gogas, H;Shapiro, F;Spriggs, DR
通讯作者：
Spriggs, DR