The mutant human ND4 subunit of complex I induces optic neuropathy in the mouse.

The mutant human ND4 subunit of complex I induces optic neuropathy in the mouse. Research Abstract Details 

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The mutant human ND4 subunit of complex I induces optic neuropathy in the mouse. Abstract Text:

Xiaoping Qi,Liang Sun,Alfred S Lewin,William W Hauswirth,John Guy,

PURPOSE: To produce a mouse model of Leber hereditary optic neuropathy. METHODS: A mutant ND4 subunit made compatible with the universal genetic code and containing an arginine-to-histidine substitution at residue 340, or a synthetic normal human ND4 gene was delivered to the mouse visual system. The expression and effects of the mutant ND4 gene on the optic nerve and cultured retinal ganglion cells was assessed by magnetic resonance imaging, immunohistochemistry, and light and transmission electron microscopy. RESULTS: The ATPc mitochondrial targeting sequence directed the allotopically expressed mutant human R340H and wild-type ND4FLAG polypeptides into mitochondria. Expression of normal human ND4 in murine mitochondria posed no ocular toxicity. In contrast, the mutant ND4 disrupted mitochondrial cytoarchitecture, elevated reactive oxygen species, induced swelling of the optic nerve head, and induced apoptosis, with a progressive demise of ganglion cells in the retina and their axons comprising the optic nerve. CONCLUSIONS: Allotopic expression of the mutant human R340H ND4 subunit of complex I replicated the hallmarks of human mitochondrial disease in the mouse. In contrast, ocular expression of the wild-type human ND4 subunit in lower mammals appears safe, suggesting that it may be useful for treatment of patients with Leber hereditary optic neuropathy.

The mutant human ND4 subunit of complex I induces optic neuropathy in the mouse. Publishing Authors By Initials

X Qi,L Sun,AS Lewin,WW Hauswirth,J Guy,

For similar investigative techniques: genetic techniques: gene transfer techniques: transfection research abstracts see: investigative techniques: genetic techniques: gene transfer techniques: transfection research

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MEDLINE DATE:

The mutant human ND4 subunit of complex I induces optic neuropathy in the mouse. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Investigative ophthalmology & visual science

VOLUME: 48

Page Numbers: 1-10

Journal Abbreviation: Invest. Ophthalmol. Vis. Sci.

ISSN: 0146-0404

DAY: 3

MONTH: Jan

YEAR: 2007

The mutant human ND4 subunit of complex I induces optic neuropathy in the mouse. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 7703701

The mutant human ND4 subunit of complex I induces optic neuropathy in the mouse. Keywords Mesh Terms:

KEYWORDS: Transfection

MESH TERMS: ultrastructure

Chemical & Substance for Abstract: The mutant human ND4 subunit of complex I induces optic neuropathy in the mouse. Information

Substance Name: Electron Transport Complex I

Registry Number: EC 1.6.5.3

Grant and Affiliation Information for The mutant human ND4 subunit of complex I induces optic neuropathy in the mouse.

AFFILIATION: Department of Ophthalmology, University of Florida College of Medicine, Gainesville, FL 32610-0284, USA.

Country: United States

AGENCY: United States NEI

GRANT: EY12335

ACRONYM: EY

MEDLINETA: Invest Ophthalmol Vis Sci

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