title: TALEN-Mediated Gene Disruption on Y Chromosome Reveals Critical Role of EIF2S3Y in Mouse Spermatogenesis.
abstract: 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.
authors.affiliation: 1 Department of Systems BioMedicine, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University , Tokyo, Japan .
authors.forename: Yohei
authors.initials: Y
authors.lastname: Matsubara
authors.forename: Tomoko
authors.initials: T
authors.lastname: Kato
authors.forename: Kenichi
authors.initials: K
authors.lastname: Kashimada
authors.forename: Hiromitsu
authors.initials: H
authors.lastname: Tanaka
authors.forename: Zhou
authors.initials: Z
authors.lastname: Zhi
authors.forename: Shizuko
authors.initials: S
authors.lastname: Ichinose
authors.forename: Shuki
authors.initials: S
authors.lastname: Mizutani
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Morio
authors.forename: Tomoki
authors.initials: T
authors.lastname: Chiba
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Ito
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Saga
authors.forename: Shuji
authors.initials: S
authors.lastname: Takada
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Asahara
mesh_terms: D000818:Animals; D004720:Endonucleases / Q000235:genetics; D015852:Eukaryotic Initiation Factor-2 / Q000235:genetics*; D018390:Gene Targeting; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D013091:Spermatogenesis / Q000235:genetics*; D013093:Spermatogonia / Q000166:cytology*; D013737:Testis / Q000166:cytology; D014998:Y Chromosome
chemical_list: D015852:Eukaryotic Initiation Factor-2; D004720:Endonucleases