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Zhirong Jiang, Sookja K. Chung, Cheng Zhou, Patrick R. Cammarata, Stephen S. M. Chung; Overexpression of Na+-Dependent Myo-inositol Transporter Gene in Mouse Lens Led to Congenital Cataract. Invest. Ophthalmol. Vis. Sci. 2000;41(6):1467-1472.
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purpose. Maintaining appropriate osmotic pressure is essential for maintaining
lens transparency. This study was performed to investigate whether high
levels of myo-inositol, one of the major organic osmolytes in the lens,
would lead to cataract development.
methods. Transgenic mouse lines carrying the bovine Na+-dependent
myo-inositol transporter (bSMIT) cDNA under the control of the mouseα
A-crystallin promoter were generated.
results. Increased bSMIT expression was accompanied by increased myo-inositol
level in the lens and increased uptake of (3H) myo-inositol
by the lens in culture. The transgenic mice developed observable
cataract under normal rearing conditions beginning at 2 to 8 weeks of
age, and the severity of cataract development was correlated to the
level of bSMIT gene expression and lens myo-inositol accumulation. For
transgenic mouse line 3352, heterozygous mice did not develop cataract,
whereas homozygous ones did. Prenatal feeding of heterozygous 3352 mice
with high myo-inositol diet led to cataract development, indicating
that cataract development was not merely due to a nonspecific effect of
SMIT overexpression. Introducing aldose reductase overexpressing
transgene into heterozygous 3352 mice also led to cataract development,
indicating that this type of cataract is primarily due to osmotic
conclusions. The present results indicate that high levels of myo-inositol and
sorbitol in the lens contribute to cataract development. This is a
useful model to study the role of osmotic stress in cataractogenesis
during lens development.
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