May 2006
Volume 47, Issue 13
ARVO Annual Meeting Abstract  |   May 2006
Defective Lens Development in the Absence of Survivin
Author Affiliations & Notes
  • M.L. Robinson
    Zoology, Miami, Oxford, OH
  • Y. Jiang
    Center for Childhood Cancer, Columbus Children's Research Institute, Columbus, OH
  • D.S. Murtagh
    Zoology, Miami, Oxford, OH
  • E.M. Conway
    Center for Transgene Technology and Gene Therapy, Flanders Interuniversity Institute for Biotechnology, University of Leuven, Leuven, Belgium
  • R.A. Altura
    Center for Childhood Cancer, Columbus Children's Research Institute, Columbus, OH
  • Footnotes
    Commercial Relationships  M.L. Robinson, None; Y. Jiang, None; D.S. Murtagh, None; E.M. Conway, None; R.A. Altura, None.
  • Footnotes
    Support  NIH Grant EY12995
Investigative Ophthalmology & Visual Science May 2006, Vol.47, 1101. doi:
  • Views
  • Share
  • Tools
    • Alerts
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      M.L. Robinson, Y. Jiang, D.S. Murtagh, E.M. Conway, R.A. Altura; Defective Lens Development in the Absence of Survivin . Invest. Ophthalmol. Vis. Sci. 2006;47(13):1101.

      Download citation file:

      © ARVO (1962-2015); The Authors (2016-present)

  • Supplements

Purpose: : Survivin is a member of the inhibitor of apoptosis protein (IAP) family that is highly expressed in cancer cells and during normal development. Survivin has been shown to function both as an apoptosis inhibitor, through interfering with caspase function, and as a chromosomal passenger protein (CPP) depending on the cell type in which it is expressed. Previous studies have demonstrated survivin expression in chick lens equatorial epithelial cells in regions of caspase–3 activity where fiber differentiation initiates, suggesting that survivin may play a role in the regulation of fiber differentiation. The purpose of these current studies was to determine the functional role of survivin in mouse lens development and/or lens cell survival.

Methods: : Mice carrying conditional (loxP–flanked) mutations in the survivin locus were used to delete survivin in the lens using two different Cre transgenes. Nestin–Cre mice express Cre recombinase in neural progenitor cells as well as in the developing lens. Le–Cre mice express Cre recombinase in the head surface ectoderm that includes the developing lens placode as well as in the pancreas. Embryos and mice, homozygous for the conditional survivin mutation and hemizygous for the Cre transgene were examined by gross observation and histology for evidence of lens abnormalities.

Results: : When survivin is deleted via the nestin–cre transgene, primary fiber cells undergo morphologically normal development but lens epithelial cells exhibit dramatic increases in apoptosis and enlargement of cell nuclei, such that few lens epithelial cells remain by E15.5. In contrast, deletion of survivin mediated by Le–Cre results in a drastically reduced lens vesicle at E 10.5 containing few cells with abnormally large nuclei. In most cases no evidence of lens cells can be seen in these mice by E12.5.

Conclusions: : Survivin is absolutely required for normal lens development. Consistently observed alterations in nuclear size in the mutant lens occur most likely as a result of the loss of a critical regulator of mitosis, suggesting that survivin acts primarily as a CPP during lens development. Loss of cell number and increased cell death may therefore be a consequence of mitotic catastrophe rather than a primary, caspase–specific effect.

Keywords: transgenics/knock-outs • apoptosis/cell death • development 

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.