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Spag6 Mutant Mice Have Defects in Development and Function of Spiral Ganglion Neurons, Apoptosis, and Higher Sensitivity to Paclitaxel

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 bip...

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Autores principales: Li, Xiaofei, Xu, Lei, Sun, Gaoying, Wu, Xianmin, Bai, Xiaohui, Li, Jianfeng, Strauss, Jerome F., Zhang, Zhibing, Wang, Haibo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5561245/
https://www.ncbi.nlm.nih.gov/pubmed/28819108
http://dx.doi.org/10.1038/s41598-017-08739-8
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author Li, Xiaofei
Xu, Lei
Sun, Gaoying
Wu, Xianmin
Bai, Xiaohui
Li, Jianfeng
Strauss, Jerome F.
Zhang, Zhibing
Wang, Haibo
author_facet Li, Xiaofei
Xu, Lei
Sun, Gaoying
Wu, Xianmin
Bai, Xiaohui
Li, Jianfeng
Strauss, Jerome F.
Zhang, Zhibing
Wang, Haibo
author_sort Li, Xiaofei
collection PubMed
description 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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spelling pubmed-55612452017-08-21 Spag6 Mutant Mice Have Defects in Development and Function of Spiral Ganglion Neurons, Apoptosis, and Higher Sensitivity to Paclitaxel Li, Xiaofei Xu, Lei Sun, Gaoying Wu, Xianmin Bai, Xiaohui Li, Jianfeng Strauss, Jerome F. Zhang, Zhibing Wang, Haibo Sci Rep Article 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. Nature Publishing Group UK 2017-08-17 /pmc/articles/PMC5561245/ /pubmed/28819108 http://dx.doi.org/10.1038/s41598-017-08739-8 Text en © The Author(s) 2017 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Li, Xiaofei
Xu, Lei
Sun, Gaoying
Wu, Xianmin
Bai, Xiaohui
Li, Jianfeng
Strauss, Jerome F.
Zhang, Zhibing
Wang, Haibo
Spag6 Mutant Mice Have Defects in Development and Function of Spiral Ganglion Neurons, Apoptosis, and Higher Sensitivity to Paclitaxel
title Spag6 Mutant Mice Have Defects in Development and Function of Spiral Ganglion Neurons, Apoptosis, and Higher Sensitivity to Paclitaxel
title_full Spag6 Mutant Mice Have Defects in Development and Function of Spiral Ganglion Neurons, Apoptosis, and Higher Sensitivity to Paclitaxel
title_fullStr Spag6 Mutant Mice Have Defects in Development and Function of Spiral Ganglion Neurons, Apoptosis, and Higher Sensitivity to Paclitaxel
title_full_unstemmed Spag6 Mutant Mice Have Defects in Development and Function of Spiral Ganglion Neurons, Apoptosis, and Higher Sensitivity to Paclitaxel
title_short Spag6 Mutant Mice Have Defects in Development and Function of Spiral Ganglion Neurons, Apoptosis, and Higher Sensitivity to Paclitaxel
title_sort spag6 mutant mice have defects in development and function of spiral ganglion neurons, apoptosis, and higher sensitivity to paclitaxel
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5561245/
https://www.ncbi.nlm.nih.gov/pubmed/28819108
http://dx.doi.org/10.1038/s41598-017-08739-8
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