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Molecular and Cellular Biology, September 2004, p. 7958-7964, Vol. 24, No. 18
0270-7306/04/$08.00+0     DOI: 10.1128/MCB.24.18.7958-7964.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Mice Deficient in the Axonemal Protein Tektin-t Exhibit Male Infertility and Immotile-Cilium Syndrome Due to Impaired Inner Arm Dynein Function

Hiromitsu Tanaka,1* Naoko Iguchi,1 Yoshiro Toyama,2 Kouichi Kitamura,1 Tohru Takahashi,1 Kazuhiro Kaseda,1 Mamiko Maekawa,2 and Yoshitake Nishimune1

Department of Science for Laboratory Animal Experimentation, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka,1 Department of Anatomy and Developmental Biology, Graduate School of Medicine, Chiba University, Chiba, Japan2

Received 19 April 2004/ Returned for modification 13 June 2004/ Accepted 26 June 2004

The haploid germ cell-specific Tektin-t protein is a member of the Tektin family of proteins that form filaments in flagellar, ciliary, and axonemal microtubules. To investigate the physiological role of Tektin-t, we generated mice with a mutation in the tektin-t gene. The homozygous mutant males were infertile, while the females were fully fertile. Sperm morphology and function were abnormal, with frequent bending of the sperm flagella and marked defects in motility. In vitro fertilization assays showed that the defective spermatozoa were able to fertilize eggs. Electron microscopic examination showed that the dynein inner arm structure was disrupted in the sperm flagella of tektin-t-deficient mice. Furthermore, homozygous mutant mice had functionally defective tracheal cilia, as evidenced by altered dynein arm morphology. These results indicate that Tektin-t participates in dynein inner arm formation or attachment and that the loss of Tektin-t results in impaired motility of both flagella and cilia. Therefore, the tektin-t gene is one of the causal genes for immotile-cilium syndrome/primary ciliary dyskinesia.

* Corresponding author. Mailing address: Department of Science for Laboratory Animal Experimentation, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamadaoka, Suita, Osaka 565-0871, Japan. Phone: 81 6-6879 8339. Fax: 81 6-6879 8339. E-mail: tanaka{at}biken.osaka-u.ac.jp.

Molecular and Cellular Biology, September 2004, p. 7958-7964, Vol. 24, No. 18
0022-538X/04/$08.00+0     DOI: 10.1128/MCB.24.18.7958-7964.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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