May 2008
Volume 49, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2008
Cdkn1b (p27Kip1) Knockout Mice: A New Model of Age-Related Nuclear Cataracts
Author Affiliations & Notes
  • Y.-B. Shui
    Dept of Ophthalmology & Visual Sciences, Washington Univ Sch of Med, St Louis, Missouri
  • F. Chu
    Dept of Ophthalmology & Visual Sciences, Washington Univ Sch of Med, St Louis, Missouri
  • C. Wu
    Dept of Ophthalmology & Visual Sciences, Washington Univ Sch of Med, St Louis, Missouri
  • D. C. Beebe
    Dept of Ophthalmology & Visual Sciences, Washington Univ Sch of Med, St Louis, Missouri
    Dept of Cell Biology and Physiology, Washington Univ Sch of Med,, St Louis, Missouri
  • Footnotes
    Commercial Relationships  Y. Shui, None; F. Chu, None; C. Wu, None; D.C. Beebe, None.
  • Footnotes
    Support  NIH EY015863
Investigative Ophthalmology & Visual Science May 2008, Vol.49, 1905. doi:https://doi.org/
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    • Get Citation

      Y.-B. Shui, F. Chu, C. Wu, D. C. Beebe; Cdkn1b (p27Kip1) Knockout Mice: A New Model of Age-Related Nuclear Cataracts. Invest. Ophthalmol. Vis. Sci. 2008;49(13):1905. doi: https://doi.org/.

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

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Abstract
 
Purpose:
 

The cyclin-dependent kinase inhibitor, p27KIP1, is involved in cell cycle control, apoptosis and cell migration and is inactivated in several kinds of cancer. Our previous study suggested that p27KIP1 was regulated by oxygen and might participate in the hypoxia-dependent inhibition of lens cell proliferation. This study describes the lens phenotype of animals in which the Cdkn1b was deleted.

 
Methods:
 

p27KIP1 (Cdkn1b) germline knockout mice and their heterozygous and wild type littermates were derived from mating heterozygotes. Morphological changes were checked by slit lamp after dilating the pupils, with a dissecting microscope, and in histological sections. Mice were dissected at different ages, the body, eyeball and lens wet weight and size were measured. Western blots were used to confirm the absence of p27KIP1 expression in the knockout lens epithelium.

 
Results:
 

Western blots confirmed the absence of p27KIP1 protein expression in the knockout lenses. Examination by slit lamp and dissecting microscope showed that Cdkn1b knockout mice had a high incidence of nuclear opacities, which increased in frequency (Fig. 1) and severity with age. Nuclear fiber cells showed early diffuse opacities, and then appeared aggregated, condensed and opaque. Lens cortical and epithelial layers appeared normal in the dissecting microscope and in H&E-stained sections. As expected from the original description of the phenotype, the body weight of Cdkn1b knockout mice was greater than wild type and heterozygous animals (p = 0.02 at 10 months of age). Surprisingly, eye and lens wet weights of the knockout mice were significantly lower than in heterozygous or wild type littermates (p < 0.0001 for both). Ongoing studies are examining proteolysis and other mechanisms that may account for the phenotype of nuclear cataract and loss of lens wet weight. We will also confirm that mutation of Cdkn1b and not another linked gene accounts for the phenotype.  

 
Conclusions:
 

Cdkn1b (p27KIP1) knockout mice may provide a useful model to study age-related nuclear cataract. The mechanism by which absence of p27KIP1 leads to nuclear cataract is under investigation.

 
Keywords: aging • transgenics/knock-outs • cataract 
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