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Biol Reprod. 2017 May 1;96(5):993-1006. doi: 10.1093/biolre/iox029.

IFT25, an intraflagellar transporter protein dispensable for ciliogenesis in somatic cells, is essential for sperm flagella formation.

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School of Public Health and Hubei Province Key Laboratory of Occupational Hazard Identification and Control, Wuhan University of Science and Technology, Wuhan, Hubei, China.
Department of Obstetrics and Gynecology, Virginia Commonwealth University, Richmond, Virginia, USA.
Department of Dermatology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Department of Gastroenterology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
Department of Andrology, Jinling Hospital, Nanjing University, School of Medicine, Nanjing, China.
Department of Computer Science, Wellesley College, Wellesley, Massachusetts, USA.
Department of Humanities and Sciences, Honor College, Virginia Commonwealth University, Richmond, Virginia, USA.
Department of Biology, Randolph-Macon College, Ashland, Virginia, USA.
Center for Research on Reproduction and Women's Health Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Comparative Biosciences, College of Veterinary Medicine, University of Illinois, Urbana, Illinois, USA.
Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, USA.


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.


ciliogenesis; flagellogenesis; germ cells; intraflagellar transport; spermiogenesis

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