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18 April 2017 IFT25, an intraflagellar transporter protein dispensable for ciliogenesis in somatic cells, is essential for sperm flagella formation
Hong Liu, Wei Li, Yong Zhang, Zhengang Zhang, Xuejun Shang, Ling Zhang, Shiyang Zhang, Yanwei Li, Andres V Somoza, Brandon Delpi, George L Gerton, James A Foster, Rex A Hess, Gregory J Pazour, Zhibing Zhang
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Abstract

Intraflagellar transport (IFT) is a conserved mechanism essential for the assembly and maintenance of most eukaryotic cilia and flagella. However, IFT25, a component of the IFT complex, is not required for the formation of cilia in somatic tissues. In mice, the gene is highly expressed in the testis, and its expression is upregulated during the final phase when sperm flagella are formed. To investigate the role of IFT25 in sperm flagella formation, the gene was specifically disrupted in male germ cells. All homozygous knockout mice survived to adulthood and did not show any gross abnormalities. However, all homozygous knockout males were completely infertile. Sperm numbers were reduced and these sperm were completely immotile. Multiple morphological abnormalities were observed in sperm, including round heads, short and bent tails, with some tails showing branched flagella and others with frequent abnormal thicknesses, as well as swollen tips of the tail. Transmission electron microscopy revealed that flagellar accessory structures, including the fibrous sheath and outer dense fibers, were disorganized, and most sperm had also lost the “9 2” microtubule structure. In the testis, IFT25 forms a complex with other IFT proteins. In Ift25 knockout testes, IFT27, an IFT25 binding partner, was missing, and IFT20 and IFT81 levels were also reduced. Our findings suggest that IFT25, although not necessary for the formation of cilia in somatic cells, is indispensable for sperm flagellum formation and male fertility in mice.

© The Authors 2017. Published by Oxford University Press on behalf of Society for the Study of Reproduction. All rights reserved. For permissions, please journals.permissions@oup.com
Hong Liu, Wei Li, Yong Zhang, Zhengang Zhang, Xuejun Shang, Ling Zhang, Shiyang Zhang, Yanwei Li, Andres V Somoza, Brandon Delpi, George L Gerton, James A Foster, Rex A Hess, Gregory J Pazour, and Zhibing Zhang "IFT25, an intraflagellar transporter protein dispensable for ciliogenesis in somatic cells, is essential for sperm flagella formation," Biology of Reproduction 96(5), 993-1006, (18 April 2017). https://doi.org/10.1093/biolre/iox029
Received: 27 November 2016; Accepted: 13 April 2017; Published: 18 April 2017
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