Azoospermia in mice with targeted disruption of the Brek/Lmtk2 (brain-enriched kinase/lemur tyrosine kinase 2) gene

Seiji Kawa, Chizuru Ito, Yoshiro Toyama, Mamiko Maekawa, Tohru Tezuka, Takahisa Nakamura, Takanobu Nakazawa, Kazumasa Yokoyama, Nobuaki Yoshida, Kiyotaka Toshimori, Tadashi Yamamoto

Research output: Contribution to journalArticlepeer-review

36 Citations (Scopus)


Brek/Lmtk2 (brain-enriched kinase/lemur tyrosine kinase 2) is a member of the Aatyk family of kinases that comprises Aatyk1, Brek/Lmtk2/Aatyk2, and Aatyk3. Although several potential roles have been proposed for Brek and other Aatyk family members, the physiological functions of these kinases remain unclear. Here, we report that Brek-/- male mice are infertile, with azoospermia. Detailed histological analysis revealed that Brek-/- germ cells differentiated normally until the round-spermatid stage, but failed to undergo the normal change in morphology to become elongated spermatids. Testicular somatic cells appeared normal in these mice. Expression of Brek in testis was restricted to the germ cells, suggesting that the maturations of germ cells in Brek-/- mice are affected in a cell-autonomous manner. On the basis of these findings, we concluded that Brek is essential for a late stage of spermatogenesis. Further clarification of the mechanism by which Brek regulates spermatogenesis may help identify new targets for reproductive contraceptives and treatments against infertility.

Original languageEnglish
Pages (from-to)19344-19349
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number51
Publication statusPublished - 2006 Dec 19
Externally publishedYes


  • BREK
  • Infertility
  • LMTK2
  • Spermatogenesis

ASJC Scopus subject areas

  • General


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