Azoospermia in mice with targeted disruption of the Brek/Lmtk2 (brain-enriched kinase/lemur tyrosine kinase 2) gene.
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.
Kawa
Seiji
S
Division of Oncology, Center for Experimental Medicine, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan.
Ito
Chizuru
C
Toyama
Yoshiro
Y
Maekawa
Mamiko
M
Tezuka
Tohru
T
Nakamura
Takahisa
T
Nakazawa
Takanobu
T
Yokoyama
Kazumasa
K
Yoshida
Nobuaki
N
Toshimori
Kiyotaka
K
Yamamoto
Tadashi
T
D000818:Animals; D053713:Azoospermia / Q000235:genetics*; D005298:Fertility / Q000235:genetics; D015151:Immunoblotting; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D046529:Microscopy, Electron, Transmission; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013091:Spermatogenesis / Q000235:genetics*; D013737:Testis / Q000648:ultrastructure
C517491:Lmtk2 protein, mouse; D017346:Protein Serine-Threonine Kinases