Targeted disruption of ATF4 discloses its essential role in the formation of eye lens fibres

Genes to Cells - Tập 3 Số 12 - Trang 801-810 - 1998
Takashi Tanaka1,2, Tohru Tsujimura3, Kohsuke Takeda1,2, Ayako Sugihara3, Akiko Maekawa1,2, Nobuyuki Terada3, Nobuaki Yoshida4, Shizuo Akira1,2
1Core Research for Evolutional Science and Technology (CREST) of Japan Science and Technology Corporation (JST)
2Department of Biochemistry, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo 663-8501, Japan
3Department of Pathology, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo 663-8501, Japan
4Research Institute Osaka Medical Center for Maternal and Child Health 840 Murodo-cho Izumi, Osaka 590-02 Japan

Tóm tắt

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.

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Genes to Cells

Tập 3 Số 12

801-810

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