A missense mutation in the murine Opa3 gene models human Costeff syndrome.

A missense mutation in the murine Opa3 gene models human Costeff syndrome. Research Abstract Details 

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A missense mutation in the murine Opa3 gene models human Costeff syndrome. Abstract Text:

Vanessa J Davies,Kate A Powell,Kathryn E White,Wanfen Yip,Vanessa Hogan,Andrew J Hollins,Jennifer R Davies,Malgorzata Piechota,David G Brownstein,Stuart J Moat,Philip P Nichols,Michael A Wride,Michael E Boulton,Marcela Votruba,

Opa3 mRNA is expressed in all tissues examined to date, but currently the function of the OPA3 protein is unknown. Intriguingly, various mutations in the OPA3 gene lead to two similar diseases in humans: autosomal dominant inherited optic atrophy and cataract (ADOAC) and a metabolic condition; type 3-methylglutaconic aciduria (MGA). Early onset bilateral optic atrophy is a common characteristic of both disorders; retinal ganglion cells are lost and visual acuity is impaired from an early age. In order to investigate the function of the OPA3 protein, we have generated a novel ENU-induced mutant mouse carrying a missense mutation in the OPA3 gene. The heterozygous mutation in exon 2, causes an amino acid change p.L122P (c.365T>C), which is predicted to alter tertiary protein structure. In the heterozygous state, the mice appear uncompromised however; in the homozygous state mice display some of the features of MGA. Visual function is severely reduced, consistent with significant loss of retinal ganglion cells and degeneration of axons in the optic nerve. In the homozygous optic nerve, there was evidence of increased mitochondrial activity, as demonstrated by the increased presence of mitochondrial marker Cytochrome C Oxidase (COX) histochemistry. Mice homozygous for the opa3(L122P) mutation also display a severe multi-systemic disease characterized by reduced lifespan (majority dying before 4 months), decreased weight, dilated cardiomyopathy, extrapyramidal dysfunction and gross neuro-muscular defects. All of these defects are synonymous with the phenotypic characteristics of Type III MGA found in humans. This model will be of major importance for future studies of the specific function of the OPA3 gene.

A missense mutation in the murine Opa3 gene models human Costeff syndrome. Publishing Authors By Initials

VJ Davies,KA Powell,KE White,W Yip,V Hogan,AJ Hollins,JR Davies,M Piechota,DG Brownstein,SJ Moat,PP Nichols,MA Wride,ME Boulton,M Votruba,

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A missense mutation in the murine Opa3 gene models human Costeff syndrome. Journal Published:

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

Journal: Brain : a journal of neurology

VOLUME: 131

Page Numbers: 368-80

Journal Abbreviation: Brain

ISSN: 1460-2156

DAY: 28

MONTH: Feb

YEAR: 2008

A missense mutation in the murine Opa3 gene models human Costeff syndrome. Information

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LANGUAGE: eng

NlmUniqueID: 372537

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Grant and Affiliation Information for A missense mutation in the murine Opa3 gene models human Costeff syndrome.

AFFILIATION: School of Optometry and Vision Sciences, Cardiff University, Maindy Road, Cathays, Cardiff CF24 4LU, UK.

Country: England

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MEDLINETA: Brain

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