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R. V. Jivrajka, F. N. Ross Cisneros, K. Kawai, A. A. Sadun, Y. H. Liu; Mouse Model of a Conditional Knockout Gene for Mitofusin 2: An Ultrastructural Examination of the Retina. Invest. Ophthalmol. Vis. Sci. 2008;49(13):4032.
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Mitofusin 2, (Mfn2), a gene that encodes for a GTPase protein in the outer mitochondrial membrane, is required for normal remodeling of mitochondrial morphology and affects their function through the process of fusion. This activity, if disrupted by a gene mutation, appears to result in Charcot-Marie-Tooth (CMT) disease with a subtype exhibiting optic atrophy. Our goal in this study was to examine the ultrastructural characteristics of the retina from a mouse model with a conditional knockout for the Mfn2 gene.
Six3-Cre::Mfn2-/- animals and littermate controls were sacrificed at specified developmental stages. Eyes were enucleated and fixed for histological analysis. Mice were divided in 3 groups at ages: 2 weeks, 1 month and 1 year and examined under EM to visualize mitochondrial morphology in random retinal sections.
The 2month old Mfn2 knockout mice show no photoreceptors and also possess an attenuated retina with the inner and out nuclear layers appear to have become "fused." Upon inspection of the mitochondria we see abundant abnormalities suggesting the possibility of autophagocytosis consistent with apoptotic changes.
Our preliminary study of mouse models demonstrates the critical role of the Mfn2 gene in the development of typical appearing mouse retinas. The inability to synthesize and use Mfn2 leads to pathologic mitochondria that results in a detectable decrease in the number of photoreceptors.
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