TALEN-Mediated Gene Disruption on Y Chromosome Reveals Critical Role of EIF2S3Y in Mouse Spermatogenesis

Stem Cells Dev. 2015 May 15;24(10):1164-70. doi: 10.1089/scd.2014.0466. Epub 2015 Feb 25.


The Y chromosome plays a critical role in spermatogenesis. Formerly, it had been difficult to generate knockout mice with specific Y chromosome mutations using conventional gene-targeting strategies. Recently, a transcription activator-like effector nuclease (TALEN) was successfully used for editing a mouse Y chromosome-linked gene. Here, we report the generation of a mouse model with a mutation in EIF2S3Y, a Y chromosome-linked gene, and analysis of its phenotype. The mouse carrying a targeted mutation of EIF2S3Y was infertile and had hypoplastic testes. Histological and electron microscopic analyses showed that differentiation of spermatogonia was arrested at the stage of spermatogonial stem cells (undifferentiated spermatogonia) and that the progression of spermatogenesis was interrupted, resulting in azoospermia. Using TALEN, we verified that EIF2S3Y performs a key function in differentiation of spermatogonial stem cells.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Endonucleases / genetics
  • Eukaryotic Initiation Factor-2 / genetics*
  • Gene Targeting
  • Male
  • Mice
  • Mice, Knockout
  • Spermatogenesis / genetics*
  • Spermatogonia / cytology*
  • Testis / cytology
  • Y Chromosome*


  • Eukaryotic Initiation Factor-2
  • Endonucleases