HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (1) Citing Articles via Google Scholar Google Scholar Articles by Yin, H. Articles by Pardue, M. T. Search for Related Content PubMed PubMed Citation Articles by Yin, H. Articles by Pardue, M. T.

Eliminating the Ant1 Isoform Produces a Mouse with CPEO Pathology but Normal Ocular Motility

¹From the Atlanta VA Medical Center, Decatur, Georgia; ²Department of Neurology, Case Western Reserve University, Cleveland, Ohio; ³Department of Neurology, Louis Stokes Cleveland VA Medical Center, Cleveland, Ohio; ⁴Department of Physiology, University of Kentucky, Lexington, Kentucky; ⁵Departments of Ophthalmology, ⁶Neurology, and ⁷Neurological Surgery, Emory University School of Medicine, Atlanta, Georgia; and ⁸Center for Molecular and Mitochondrial Medicine and Genetics, University of California, Irvine, California.

PURPOSE. The adenine nucleotide transporter 1 gene (ANT1) encodes an inner mitochondrial membrane protein that transports ATP into the cell. Mutations within ANT1 produce a syndrome of chronic progressive external ophthalmoplegia (CPEO) in humans. Ant1 knockout (Ant1^–/–) mice develop cardiomyopathy and mitochondrial myopathy of limb muscles. Because the extraocular muscles (EOM) are preferentially affected in human CPEO, the objective of this study was to determine whether Ant1^–/– mice also exhibit an EOM mitochondrial myopathy.

METHODS. ANT isoform expression of isolated EOMs, EOM morphology and mitochondrial content, mitochondrial structure and function, ocular motility in intact mice, and contractile performance in isolated muscle preparations were examined.

RESULTS. Ant1^–/– EOMs had the typical appearance of mitochondrial myopathy, including increase in mitochondrial size, number, and oxidative phosphorylation (OXPHOS) staining. However, there were no measurable ocular motor abnormalities in intact Ant1^–/– mice, and their isolated EOMs did not show evidence of increased fatigability. EOMs of wild-type mice exhibited higher levels of Ant2 mRNA compared with hindlimb muscle, which may compensate for the Ant1 loss in mutant mouse EOMs and account for the normal EOM function.

CONCLUSIONS. The Ant1^–/– mice provide a model in which to study CPEO pathology and compensatory mechanisms.

This article has been cited by other articles:

				A. Omar and L. N. Johnson Tetracycline delays ocular motility decline in chronic progressive external ophthalmoplegia Neurology, April 3, 2007; 68(14): 1159 - 1160. [Full Text] [PDF]