Abstract
Costeff Syndrome, which is caused by mutations in the OPTIC ATROPHY 3 (OPA3) gene, is an early-onset syndrome characterized by urinary excretion of 3-methylglutaconic acid (MGC), optic atrophy and movement disorders, including ataxia and extrapyramidal dysfunction. The OPA3 protein is enriched in the inner mitochondrial membrane and has mitochondrial targeting signals, but a requirement for mitochondrial localization has not been demonstrated. We find zebrafish opa3 mRNA to be expressed in the optic nerve and retinal layers, the counterparts of which in humans have high mitochondrial activity. Transcripts of zebrafish opa3 are also expressed in the embryonic brain, inner ear, heart, liver, intestine and swim bladder. We isolated a zebrafish opa3 null allele for which homozygous mutants display increased MGC levels, optic nerve deficits, ataxia and an extrapyramidal movement disorder. This correspondence of metabolic, ophthalmologic and movement abnormalities between humans and zebrafish demonstrates a phylogenetic conservation of OPA3 function. We also find that delivery of exogenous Opa3 can reduce increased MGC levels in opa3 mutants, and this reduction requires the mitochondrial localization signals of Opa3. By manipulating ...Continue Reading
References
Apr 1, 1989·Neurology·H CosteffH Savir
Jan 1, 1985·Methods in Enzymology·B R Landau, H Brunengraber
Jan 1, 1981·Annual Review of Biochemistry·G J Schroepfer
Feb 1, 1994·Developmental Medicine and Child Neurology·O N ElpelegK M Gibson
May 1, 1995·Pediatric Research·R I Kelley, L Kratz
Mar 1, 1993·Pediatric Neurology·K M GibsonR I Kelley
Jul 1, 1995·Developmental Dynamics : an Official Publication of the American Association of Anatomists·C B KimmelT F Schilling
Apr 1, 1996·Nature Genetics·S BioneD Toniolo
Dec 9, 1996·The Journal of Comparative Neurology·R R BernhardtM Schachner
Jul 9, 1999·The British Journal of Ophthalmology·R M AndrewsD M Turnbull
Jul 17, 1999·Journal of Inherited Metabolic Disease·R A WeversF J Gabreëls
Aug 18, 1999·Archives of Disease in Childhood·A NissenkornT Lerman-Sagie
Jul 24, 2001·Journal of Neurocytology·E Mohr, D Richter
Sep 19, 2001·The Journal of Clinical Investigation·B U FitzkyG S Tint
Oct 23, 2001·American Journal of Human Genetics·Y AniksterO Elpeleg
Jul 19, 2002·Analytical Biochemistry·Nae-Cherng YangMiao-Lin Hu
Jul 20, 2002·Molecular Genetics and Metabolism·Robert KletaYair Anikster
Oct 2, 2002·Annals of Internal Medicine·Paul S PhillipsUNKNOWN Scripps Mercy Clinical Research Center
Nov 16, 2002·American Journal of Human Genetics·Lodewijk IJlstRonald J A Wanders
Jul 17, 2003·The Journal of Biological Chemistry·Sandrine Da CruzJean-Claude Martinou
Feb 13, 2004·Developmental Cell·Juanita L ThorpeSteven A Farber
Sep 3, 2004·Journal of Medical Genetics·P ReynierD Bonneau
Oct 1, 2005·Molecular Genetics and Metabolism·Marjan HuizingYair Anikster
Jun 24, 2006·Circulation Research·Zaza KhuchuaArnold W Strauss
Jul 11, 2006·Methods : a Companion to Methods in Enzymology·Raman SoodP Paul Liu
Sep 15, 2006·American Journal of Physiology. Cell Physiology·Min WuDavid A Ferrick
Jul 3, 2007·The Journal of Experimental Biology·Harold A Burgess, Michael Granato
Jan 29, 2008·Brain : a Journal of Neurology·Vanessa J DaviesMarcela Votruba
Nov 4, 2008·Briefings in Functional Genomics & Proteomics·Li-En JaoShawn M Burgess
Nov 6, 2008·Journal of Inherited Metabolic Disease·G HoJ Christodoulou
Mar 26, 2009·Human Mutation·Marc FerréPatrizia Amati-Bonneau
Aug 12, 2009·Proceedings of the National Academy of Sciences of the United States of America·Jia YaoRoberta Diaz Brinton
Dec 8, 2009·Current Biology : CB·Natalia GebertNikolaus Pfanner
Mar 31, 2010·Molecular Genetics and Metabolism·Marjan HuizingYair Anikster
Citations
Oct 1, 2010·Journal of Inherited Metabolic Disease·Saskia B WortmannEva Morava
Jan 9, 2013·Journal of Inherited Metabolic Disease·Saskia B WortmannRon A Wevers
Aug 8, 2012·Human Molecular Genetics·Timothy WellsMarcela Votruba
Nov 3, 2011·Disease Models & Mechanisms·Timo FriedrichGerald B Downes
Jan 11, 2014·Journal of Inherited Metabolic Disease·Betty Su, Robert O Ryan
Jan 29, 2013·Journal of Inherited Metabolic Disease·Saskia B WortmannRon A Wevers
Sep 24, 2013·Translational Research : the Journal of Laboratory and Clinical Medicine·Shelby L SteeleJason N Berman
Jun 14, 2013·British Journal of Pharmacology·Brígida R PinhoJorge M A Oliveira
Feb 7, 2015·American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics : the Official Publication of the International Society of Psychiatric Genetics·S SoferS Hassin-Baer
Sep 10, 2014·Journal of Neurology·Gilad YahalomSharon Hassin-Baer
Nov 30, 2010·Progress in Retinal and Eye Research·Patrick Yu-Wai-ManPatrick F Chinnery
Oct 7, 2010·Genomics·Marta Owczarek-LipskaMartin H Braunschweig
Jul 28, 2016·Frontiers in Molecular Neuroscience·Robert A KozolJulia E Dallman
Jul 19, 2016·Scientific Reports·Wuhong PeiShawn M Burgess
Jan 5, 2017·Cold Spring Harbor Molecular Case Studies·Stephanie C BourneWilliam T Gibson
May 18, 2019·International Journal of Molecular Sciences·Gianluca FichiVittoria Petruzzella
Apr 20, 2016·Journal of Inherited Metabolic Disease·Nikita Ikon, Robert O Ryan
Nov 24, 2015·Annual Review of Vision Science·Brian A Link, Ross F Collery
May 24, 2019·Neurology. Genetics·Alejandro HorgaMary M Reilly
Apr 24, 2016·Human Molecular Genetics·Alice E NaveinTimothy Wells
Oct 19, 2019·Biochimie·Joseph VamecqVéronique Kruys
Mar 18, 2020·Journal of Natural Products·Dale TranterDominic Hoepfner
Sep 3, 2021·The Science of the Total Environment·Yuming ChenWeidong Wu