Ocular Abnormalities and Cardiomyopathy Associated with Mutations in the Mouse Large Gene

Abstract

Abstract: : Purpose: A mutation within the Large gene has recently been identified as the mouse myodystrophy (myd) mutation. We have characterized a new allele of myd, named veils (vls), and report two unique features not described previously, cardiomyopathy and ocular abnormalities. Methods: We have performed positional cloning aproach, candidate gene analysis, Northern blot analysis, Histochemical analysis, Fluorescein angiography, ERG, Electron microscopic analysis and Immunohistochemistry. Results: Examination of Large cDNA from veils mice showed a deletion of exons 3 through 5, causing a frameshift after amino acid 35, which leads to a premature stop codon following amino acid 37. The ocular abnormalities include persistent hyaloid vessels, vitreal fibroplasia and vascularization, retinal dysplasia, and progressive peripheral retinal degeneration. Electroretinograms for both rods and cones are abnormal. we observe that the ILM of the retina from veils mice is disrupted and the cytoplasm of Müller cells extends into the vitreal space. Immunohistochemical analysis reveals that several components of the ILM (α- and ß-dystroglycan, utrophin and dystrophin) are absent and only a weak staining of laminin is observed in veils retina. Conclusions: Our data suggest that mutations within the Large gene disturb the assemble of the dystrophin glycoprotein complex in the ILM of the retina.

Keywords: animal model • ganglion cells • molecular biology