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J. M. Fadool, K. Alvarez-Delfin, A. Csizinszky, W. E. Hiller, A. C. Morris; Histological and Molecular Characterization of Lens Defects in Larval Zebrafish. Invest. Ophthalmol. Vis. Sci. 2007;48(13):2448.
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© ARVO (1962-2015); The Authors (2016-present)
Recognizing the potential of forward genetic screens for identifying novel genes and novel gene functions during development, we are continuing a comprehensive genetic screen to identify recessive mutations in free-swimming larval zebrafish that would serve as models of congenital defects and hereditary diseases of the anterior chamber and lens.
In collaboration with Mary Mullins and Michael Granato at the University of Pennsylvania, the larvae of inbred lines of chemically-mutagenized zebrafish were screened to uncover late-onset, recessive mutations affecting eye morphology, the cornea and the clarity and position of the lens. Mutant phenotypes were further characterized by histological, immunocytochemical and molecular methods. The mutagenesis strategy incorporated a mapping panel to facilitate linkage analysis of the mutated loci.
We have recovered numerous recessive mutations that affected the size of the lens or lens clarity, resulted in lens degeneration or produced an ectopic lens. The most common phenotype is lens cataract or opacity of the lens. The second most frequent phenotype is formation of vesicles between the lens fiber cells and the epithelium, suggesting alteration in solute or water transport activity. In the previously described line that shows ectopic lens, histological analysis revealed a loss of integrity of the lens epithelium and rupture of the lens capsule. Surprisingly, the remnants of the epithelium continue to proliferate. Linkage analysis positioned the locus on chromosome 7 and candidate genes are being tested. For several of the mutant loci, the larvae display few or no other defects and can be grown to adults.
We provide a strategy for the identification of highly specific mutations affecting the visual system of zebrafish. As the desired phenotypes are not present until later stages of development, it is hypothesized that some of the identified mutations will serve as much needed models of human congenital defects.
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