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Targeted disruption of ATF4 discloses its essential role in the formation of eye lens fibres
Author(s) -
Tanaka Takashi,
Tsujimura Tohru,
Takeda Kiyoshi,
Sugihara Ayako,
Maekawa Akiko,
Terada Nobuyuki,
Yoshida Nobuaki,
Akira Shizuo
Publication year - 1998
Publication title -
genes to cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.912
H-Index - 115
eISSN - 1365-2443
pISSN - 1356-9597
DOI - 10.1046/j.1365-2443.1998.00230.x
Subject(s) - atf4 , biology , transcription factor , microbiology and biotechnology , lens fiber , crystallin , lens (geology) , gene , genetics , paleontology , nucleus
Background : Activating transcription factor‐4 (ATF4)—also termed CREB2, C/ATF, and TAXREB67—is a basic‐leucine zipper (bZip) transcription factor that belongs to the ATF/CREB family. In addition to its own family members, ATF4 can also form heterodimers with other related but distinct bZIP proteins such as the C/EBP, AP‐1 and Maf families, which may give rise to a variety of combinatorial diversity in gene regulation. In order to assess the in vivo essential role of ATF4, we have generated mice lacking ATF4 by gene targeting. Results : ATF4‐deficient mice exhibited severe microphthalmia. Although ATF4‐deficient eyes revealed a normal gross lens structure up to embryonic day 14.5, later on the ATF4‐deficient lens, degenerated due to apoptosis without the formation of lens secondary fibre cells. Retinal development was normal in the mutant mice. The lens‐specific expression of ATF4 in the mutant mice led not only to the recovery of lens secondary fibres but also to the induction of hyperplasia of these fibres. Conclusion : These results demonstrated that ATF4 is essential for the later stages of lens fibre cell differentiation.