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J.M. Fadool, K. Alvarez–Delfin, A.C. deCarvalho, A.C. Morris; Genetic Screen of Free–Swimming Zebrafish Identifies Loci Essential For Maintenance of the Crystalline Lens . Invest. Ophthalmol. Vis. Sci. 2006;47(13):2517.
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© ARVO (1962-2015); The Authors (2016-present)
The zebrafish (Danio rerio) is a valuable model to uncover genes essential for the development and function of the vertebrate visual system. Recognizing the potential of forward genetic screens for identifying novel genes and novel gene functions, we undertook a comprehensive genetic screen to identify recessive mutations leading to defects of the visual system in free–swimming larvae and adult zebrafish. This facet of the screen focuses on mutations affecting the anterior segment, eye shape and the crystalline lens.
In collaboration with Mary Mullins and Michael Ganato at the University of Pennsylvania, the third generation larvae of inbred, chemically mutagenized, zebrafish were reared to adults. This provided the unprecedented opportunity to uncover late onset, recessive mutations affecting eye morphology, the cornea and the lens. Furthermore, the third generation adults were inbred, and we screened for changes in the visual system of the 5 day old free–swimming larvae. The mutagenesis strategy incorporated a mapping panel to facilitate linkage analysis of the mutated genes.
In the initial screen of more than 300 genomes, we recovered recessive mutations that affected the size of the lens or lens clarity, resulted in lens degeneration or produced ectopic lens. Several of these are adult viable phenotypes. Interestingly, in one line, the ectopic lens was replaced by the regeneration of new lens from the remnants of the lens epithelium.
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 would serve as much needed models of human dystrophies and congenital defects. Furthermore, the regeneration of the lens in one mutant line is indicative of the robust and wide spread regenerative capacity of the teleost system.
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