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

Genes Cells. 1998 Dec;3(12):801-10. doi: 10.1046/j.1365-2443.1998.00230.x.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Activating Transcription Factor 4
  • Animals
  • Apoptosis
  • Cell Differentiation / genetics
  • Epithelium / embryology
  • Epithelium / pathology
  • Epithelium / physiology
  • Eye / cytology
  • Eye / embryology
  • Eye / growth & development
  • Eye / pathology
  • Gene Expression Regulation, Developmental
  • Hyperplasia
  • Lens, Crystalline / embryology*
  • Lens, Crystalline / pathology
  • Lens, Crystalline / physiology
  • Mice
  • Mice, Mutant Strains
  • Mice, Transgenic
  • Retina / embryology
  • Transcription Factors / genetics*


  • Transcription Factors
  • Activating Transcription Factor 4