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F. N. Ross-Cisneros, R. V. Jivrajka, K. Kawai, Y. H. Liu, A. A. Sadun; An Ultrastructural Examination of the Optic Nerve in a Mouse Model for a Conditional Knockout Gene in Mitofusin 2. Invest. Ophthalmol. Vis. Sci. 2008;49(13):5383. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
To investigate the ultrastructural characteristics of the optic nerve in a mouse model with a conditional knockout (CKO) for the mitofusin (Mfn) 2 gene.
Two month old Mfn2 conditional knockout mice and controls were humanely sacrificed according to the ARVO Statement for the Use of Animals in Ophthalmic and Visual Research. Mice were enucleated and eyes with optic nerves were immersion-fixed in mixed aldehydes. Retrobulbar optic nerves were dissected away from the globe as cross-section profiles and processed for embedding into plastic blocks. Thin sections were obtained, stained with uranyl acetate and lead citrate, and examined on a transmission electron microscope (TEM).
Control optic nerves appeared normal. Mfn2 CKO nerves possessed several degenerated axonal profiles. Several axons displayed thin myelin or were completely denuded. Many of the intact axons exhibited numerous mitochondria of various sizes. The mitochondria would often display evidence of abnormal cristae that appeared either vesicular, condensed, or absent. There were numerous macrophages. There were several cells with pyknotic nuclei which appeared to be oligodendroglia undergoing apoptotic changes.
The Mfn2 gene is required for normal mitochondrial fusion which, if mutated, can lead to neurological disorders involving neuropathy and optic atrophy as observed in Charcot-Marie-Tooth disease. This CKO mouse model for the Mfn2 gene may serve as a tool to observe how the mitofusins contribute to optic atrophy and other neurological disorders associated with aberrant mitochondrial fusion.
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