A mouse model for mitochondrial myopathy and cardiomyopathy resulting from a deficiency in the heart/muscle isoform of the adenine nucleotide translocator

Graham, Brett H.; Waymire, Katrina G.; Cottrell, Barbara A.; Trounce, Ian A.; MacGregor, Grant R.; Wallace, Douglas C.

doi:10.1038/ng0797-226

Cited by 517 publications

(458 citation statements)

References 45 publications

Supporting

Mentioning

435

Contrasting

Unclassified

Order By: Relevance

“…The Ant1 genotype of animals was determined by differential PCR. 9 Nucleic acids were isolated from soleus and gastrocnemius muscle using Trizol s (Life Technologies), and RNA, DNA and protein were collected taking into account the small samples available (1 Â 10 6 myocytes, 250 mg of muscle tissue). RNA expression of AAV-ANT1 was assayed by semiquantitative RT-PCR (Roche).…”

Section: Aav-mediated Gene Transfer Of Ant In Mousementioning

confidence: 99%

“…Western blots were developed by using affinity-purified polyclonal antibodies. 9 The protein content of cell and tissue lysates was determined by Lowry protein assay (Pierce). Protein (25 mg) of total tissue lysate or 15 mg of isolated mitochondrial lysate were separated using 10% TG-SDS-PAGE in an MESbuffer system (NOVEX/Invitrogen), blotted onto nitrocellulose membranes (Biorad) and the blots stained with Ponceau S (Sigma).…”

Section: Aav-mediated Gene Transfer Of Ant In Mousementioning

confidence: 99%

“…This recessive mutant results in a massive proliferation of muscle mitochondria and the hyperinduction of mitochondrial enzymes along with increased mitochondrial DNA (mtDNA) rearrangements. 9 Hence, the ANT1-deficient mouse provides an excellent model for exploring therapeutic approaches for mitochondrial myopathy.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Adeno-associated virus-mediated gene transfer of the heart/muscle adenine nucleotide translocator (ANT) in mouse

Flierl

Coşkun

et al. 2005

Gene Ther

View full text Add to dashboard Cite

Section: Aav-mediated Gene Transfer Of Ant In Mousementioning

confidence: 99%

Section: Aav-mediated Gene Transfer Of Ant In Mousementioning

confidence: 99%

See 1 more Smart Citation

Adeno-associated virus-mediated gene transfer of the heart/muscle adenine nucleotide translocator (ANT) in mouse

Flierl

Coşkun

et al. 2005

Gene Ther

View full text Add to dashboard Cite

“…Ant1 knockout mice were born apparently normal but developed severe exercise intolerance and cardiac hypertrophy in adult stages accompanied with skeletal and cardiac myopathy. 19 Ant4 knockout mice were also born and grew normally without showing any abnormality except male infertility. 16 Spermatogenesis was severely impaired by Ant4 gene disruption, and the mice failed to generate mature spermatozoa.…”

mentioning

confidence: 99%

Mitochondrial ATP transporter Ant2 depletion impairs erythropoiesis and B lymphopoiesis

Seo

et al. 2015

Cell Death Differ

View full text Add to dashboard Cite

Adenine nucleotide translocases (ANTs) transport ADP and ATP through mitochondrial inner membrane, thus playing an essential role for energy metabolism of eukaryotic cells. Mice have three ANT paralogs, Ant1 (Slc25a4), Ant2 (Slc25a5) and Ant4 (Slc25a31), which are expressed in a tissue-dependent manner. While knockout mice have been characterized with Ant1 and Ant4 genes, which resulted in exercise intolerance and male infertility, respectively, the role of the ubiquitously expressed Ant2 gene in animal development has not been fully demonstrated. Here, we generated Ant2 hypomorphic mice by targeted disruption of the gene, in which Ant2 expression is largely depleted. The mice showed apparently normal embryonic development except pale phenotype along with a reduced birth rate. However, postnatal growth was severely retarded with macrocytic anemia, B lymphocytopenia, lactic acidosis and bloated stomach, and died within 4 weeks. Ant2 depletion caused anemia in a cell-autonomous manner by maturation arrest of erythroid precursors with increased reactive oxygen species and premature deaths. B-lymphocyte development was similarly affected by Ant2 depletion, and splenocytes showed a reduction in maximal respiration capacity and cellular ATP levels as well as an increase in cell death accompanying mitochondrial permeability transition pore opening. In contrast, myeloid, megakaryocyte and T-lymphocyte lineages remained apparently intact. Erythroid and B-cell development may be particularly vulnerable to Ant2 depletion-mediated mitochondrial dysfunction and oxidative stress.

show abstract

“…All of these disorders are transmitted as autosomal recessive traits and there have been great strides in our understanding of their molecular bases (DeVivo et al, 1996). The adenine nucleotide translocator (Ant) deserves special mention because recently a "knockout" mouse was generated with markedly deficient expression of the muscle/heart isoform of Ant (Antl) (Graham et at., 1997). This is the first animal model with the morphological and biochemical features of mitochondrial myopathy and cardiomyopathy.…”

mentioning

confidence: 99%

Mitochondrial disorders

DiMauro

Tanji

1997

Jap J Human Genet

View full text Add to dashboard Cite

SummaryIn this minireview, we attempt to survey the three main group of mitochondrial disorders, defects of nuclear DNA, defects of mitochondrial DNA, and defects of intergenomic signaling, with emphasis on recent contributions and pathogenetic mechanisms. In so doing, we have tried to point out some of the numerous unsolved problems in genotype/phenotype correlation and to indicate future directions of research. Key Words mitochondria, mitochondrial DNA, intergenomic signaling, respiratory chain, mitochondrial encephalomyopathiesThe fascinating and still unfolding story of mitochondrial disorders is not only a "tale of two genomes," but also a tale of their sometimes less than harmonious interaction. Thus, we have to review succinctly three types of human diseases: 1) Defects of nuclear genes, inherited as mendelian traits; 2) Defects of mitochondrial genes, which can be sporadic conditions or maternally-inherited disorders; and 3) Defects of intergenomic communication, in which the still unknown culprits are nuclear genes and inheritance is mendelian. Though in our review we will consider these three groups in sequence, a unified biomolecular classification of the mitochondrial disorders, including acquired conditions, is offered in Table I. Because of the concise nature of these minireviews, we will limit references to the most recent contributions. Other references are provided in recent comprehensive reviews, including three chapters in a row in the 2nd edition of The

show abstract

A mouse model for mitochondrial myopathy and cardiomyopathy resulting from a deficiency in the heart/muscle isoform of the adenine nucleotide translocator

Cited by 517 publications

References 45 publications

Adeno-associated virus-mediated gene transfer of the heart/muscle adenine nucleotide translocator (ANT) in mouse

Adeno-associated virus-mediated gene transfer of the heart/muscle adenine nucleotide translocator (ANT) in mouse

Mitochondrial ATP transporter Ant2 depletion impairs erythropoiesis and B lymphopoiesis

Mitochondrial disorders

Contact Info

Product

Resources

About