Skip Navigation

This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (24)
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Agostino, A.
Right arrow Articles by Zeviani, M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Agostino, A.
Right arrow Articles by Zeviani, M.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Human Molecular Genetics, 2003, Vol. 12, No. 4 399-413
© 2003 Oxford University Press

Constitutive knockout of Surf1 is associated with high embryonic lethality, mitochondrial disease and cytochrome c oxidase deficiency in mice

Alessandro Agostino1, Federica Invernizzi1, Cecilia Tiveron2, Gigliola Fagiolari3, Alessandro Prelle3, Eleonora Lamantea1, Alessio Giavazzi4, Giorgio Battaglia4, Laura Tatangelo2, Valeria Tiranti1 and Massimo Zeviani1,*

1Unit of Molecular Neurogenetics, Pierfranco and Luisa Mariani Center for the Study of Children's Mitochondrial Disorders, Istituto Nazionale Neurologico ‘C. Besta’-IRCCS, Milano, Italy, 2Laboratory of Animal Models, Istituto Regina Elena, Roma, Italy, 3Dino Ferrari Center, Department of Neuroscience, Ospedale Maggiore Policlinico-IRCCS, Milano, Italy and 4Laboratory of Molecular Neuroanatomy, Unit of Experimental Neurophysiology, Istituto Nazionale Neurologico ‘C. Besta’-IRCCS, Milano, Italy

Received October 29, 2002; Revised December 16, 2002; Accepted December 17, 2002

We report here the creation of a constitutive knockout mouse for SURF1, a gene encoding one of the assembly proteins involved in the formation of cytochrome c oxidase (COX). Loss-of-function mutations of SURF1 cause Leigh syndrome associated with an isolated and generalized COX deficiency in humans. The murine phenotype is characterized by the following hallmarks: (1) high post-implantation embryonic lethality, affecting ~90% of the Surf1-/- individuals; (2) early-onset mortality of post-natal individuals; (3) highly significant deficit in muscle strength and motor performance; (4) profound and isolated defect of COX activity in skeletal muscle and liver, and, to a lesser extent, heart and brain; (5) morphological abnormalities of skeletal muscle, characterized by reduced histochemical reaction to COX and mitochondrial proliferation; (6) no obvious abnormalities in brain morphology, reflecting the virtual absence of overt neurological symptoms. These results indicate a function for murine Surf1 protein (Surf1p) specifically related to COX and recapitulate, at least in part, the human phenotype. This is the first mammalian model for a nuclear disease gene of a human mitochondrial disorder. Our model constitutes a useful tool to investigate the function of Surf1p, help understand the pathogenesis of Surf1p deficiency in vivo, and evaluate the efficacy of treatment.

* To whom correspondence should be addressed at: Unit of Molecular Neurogenetics, National Neurological Institute ‘Carlo Besta’, via Temolo 4, 20126 Milan, Italy. Tel: +39 022394630; Fax: +39 022394619; Email: zeviani{at}tin.it


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 Genes Dev.Home page
D. C. Wallace and W. Fan
The pathophysiology of mitochondrial disease as modeled in the mouse
Genes & Dev., August 1, 2009; 23(15): 1714 - 1736.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
M. Son, S. C. Leary, N. Romain, F. Pierrel, D. R. Winge, R. G. Haller, and J. L. Elliott
Isolated Cytochrome c Oxidase Deficiency in G93A SOD1 Mice Overexpressing CCS Protein
J. Biol. Chem., May 2, 2008; 283(18): 12267 - 12275.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Pathol.Home page
M Pronicki, E Matyja, D Piekutowska-Abramczuk, T Szymanska-Debinska, A Karkucinska-Wieckowska, E Karczmarewicz, W Grajkowska, T Kmiec, E Popowska, and J Sykut-Cegielska
Light and electron microscopy characteristics of the muscle of patients with SURF1 gene mutations associated with Leigh disease
J. Clin. Pathol., April 1, 2008; 61(4): 460 - 466.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
K. N. Baden, J. Murray, R. A. Capaldi, and K. Guillemin
Early Developmental Pathology Due to Cytochrome c Oxidase Deficiency Is Revealed by a New Zebrafish Model
J. Biol. Chem., November 30, 2007; 282(48): 34839 - 34849.
[Abstract] [Full Text] [PDF]

Home page
 GeneticsHome page
W. Liu, R. Gnanasambandam, J. Benjamin, G. Kaur, P. B. Getman, A. J. Siegel, R. D. Shortridge, and S. Singh
Mutations in Cytochrome c Oxidase Subunit VIa Cause Neurodegeneration and Motor Dysfunction in Drosophila
Genetics, June 1, 2007; 176(2): 937 - 946.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Biol. CellHome page
P. B. Bokko, L. Francione, E. Bandala-Sanchez, A. U. Ahmed, S. J. Annesley, X. Huang, T. Khurana, A. R. Kimmel, and P. R. Fisher
Diverse Cytopathologies in Mitochondrial Disease Are Caused by AMP-activated Protein Kinase Signaling
Mol. Biol. Cell, May 1, 2007; 18(5): 1874 - 1886.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
C. Dell'Agnello, S. Leo, A. Agostino, G. Szabadkai, C. Tiveron, A. Zulian, A. Prelle, P. Roubertoux, R. Rizzuto, and M. Zeviani
Increased longevity and refractoriness to Ca2+-dependent neurodegeneration in Surf1 knockout mice
Hum. Mol. Genet., February 15, 2007; 16(4): 431 - 444.
[Abstract] [Full Text] [PDF]

Home page
 J Child NeurolHome page
S. K.H. Tay, S. Sacconi, H. Ohran Akman, J. F. Morales, A. Morales, D. C. De Vivo, S. Shanske, E. Bonilla, and S. DiMauro
Unusual Clinical Presentations in Four Cases of Leigh Disease, Cytochrome C Oxidase Deficiency, and SURF1 Gene Mutations
J Child Neurol, August 1, 2005; 20(8): 670 - 674.
[Abstract] [PDF]

Home page
 J. Biol. Chem.Home page
D. Smith, J. Gray, L. Mitchell, W. E. Antholine, and J. P. Hosler
Assembly of Cytochrome-c Oxidase in the Absence of Assembly Protein Surf1p Leads to Loss of the Active Site Heme
J. Biol. Chem., May 6, 2005; 280(18): 17652 - 17656.
[Abstract] [Full Text] [PDF]

Home page
 BrainHome page
M. Zeviani and S. Di Donato
Mitochondrial disorders
Brain, October 1, 2004; 127(10): 2153 - 2172.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
S. L. Williams, I. Valnot, P. Rustin, and J.-W. Taanman
Cytochrome c Oxidase Subassemblies in Fibroblast Cultures from Patients Carrying Mutations in COX10, SCO1, or SURF1
J. Biol. Chem., February 27, 2004; 279(9): 7462 - 7469.
[Abstract] [Full Text] [PDF]

Home page
 Annals of Clinical & Laboratory ScienceHome page
E. Fosslien
Mitochondrial Medicine - Cardiomyopathy Caused by Defective Oxidative Phosphorylation
Ann. Clin. Lab. Sci., October 1, 2003; 33(4): 371 - 395.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurol. Neurosurg. PsychiatryHome page
P F Chinnery and E A Schon
Mitochondria
J. Neurol. Neurosurg. Psychiatry, September 1, 2003; 74(9): 1188 - 1199.
[Abstract] [Full Text] [PDF]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.