• PMID: 11784110
• Gene Name: LIMK2
• Condition: Plays a role in proper progression of spermatogenesis by regulation of cofilin activity and/or localization in germ cells
• Association: Associated
• Sex: Male
• Infertility type: Male infertility
• Other associated phenotypes: Plays a role in proper progression of spermatogenesis by regulation of cofilin activity and/or localization in germ cells

Impaired spermatogenic ability of testicular germ cells in mice deficient in the LIM-kinase 2 gene

Takahashi H, Koshimizu U, Miyazaki J, Nakamura T.

LIM-Kinase (LIMK), including LIMK1 and LIMK2, is the only known catalytic protein among LIM-family molecules. It is well known that LIMK phosphorylates and inactivates cofilin, an actin-depolymerizing factor regulating actin reorganization, while in vivo functions have remained to be elucidated. In the present study, we generated Limk2 gene-deficient mice in which three LIMK2 isoforms were disrupted in a Cre-mediated fashion. Impaired cofilin phosphorylation was clearly observed in Limk2-/- fibroblasts stimulated with bradykinin or lysophosphatidic acid, thereby suggesting that Cdc42 or Rho-dependent LIMK activation did not occur. However, Limk2-/- mice did not exhibit embryonic lethality or any phenotypic abnormalities in postnatal growth and development, except for spermatogenesis in the testis. The testes of Limk2-/- mice were smaller in size and partial degeneration of spermatogenic cells in the seminiferous tubules was apparent in association with increased apoptosis. In addition, the viability of Limk2-/- spermatogenic cells, when cultured under stressed conditions, was diminished. Furthermore, the potential for germ cells to differentiate in a regenerative state was severely impaired in Limk2-/- testis. Experimental hyperthermia induced impairment of ADF/cofilin phosphorylation and the formation of intranuclear cofilin inclusions in mutant germ cells. Based on these findings, we propose that LIMK2, especially the testis-specific isoform tLIMK2, plays an important role in proper progression of spermatogenesis by regulation of cofilin activity and/or localization in germ cells. CI - (c)2002 Elsevier Science. FAU - Takahashi, Hisaaki AU - Takahashi H AD - Division of Molecular Regenerative Medicine, Course of Advanced Medicine B7, Osaka University Graduate School of Medicine, Suita, Osaka, 565-0871, Japan. FAU - Koshimizu, Uichi AU - Koshimizu U FAU - Miyazaki, Jun-ichi AU - Miyazaki J