Cited by 124Mitochondrial Function and PathologyDNA Repair MechanismsGenetics, Aging, and Longevity in Model Organisms

Construction of transgenic mice with tissue-specific acceleration of mitochondrial DNA mutagenesis

Zhang, Dekui, Mott, Justin L., Chang, Shin-Wen, Denniger, Grace, Feng, Zehua, Zassenhaus, Hans Peter·2000·Genomics

Abstract

Transgenic mice having rapid accumulation of mitochondrial DNA (mtDNA) mutations specifically in the heart were created. These mice contained a transgene encoding a proofreading-deficient, mouse mitochondrial DNA polymerase (pol gamma) driven by the promoter for the cardiac-specific alpha-myosin heavy chain. Starting shortly after birth greater than 95% of all pol gamma mRNA in the heart was transgene derived; expression in other tissues was low or absent. Mutations in cardiac mtDNA began to accumulate by 7 days after birth. At 1 month of age the frequency of point mutations was 0.014% as determined by DNA sequencing of cloned mtDNA. By long-extension PCR multiple different deletion mutations that had removed several thousand basepairs of genomic sequence were also detected. Sequencing of two deletion molecules showed that one was flanked at the breakpoint by direct repeat sequences. The expression of proofreading-deficient pol gamma had no apparent deleterious effect on mitochondrial DNA and protein content, gene expression, or respiratory function. However, associated with the rise in mtDNA mutation levels was the development of cardiomyopathy as evidenced by enlarged hearts in the transgenic mice. These mice may prove to be useful models to study the pathogenic effects of elevated levels of mitochondrial DNA mutations in specific tissues.

Integrity signals

Registry

Crossref · 10.1006/geno.2000.6333

Cites

45 of 45 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • In mice, transgenic overexpression of exonuclease-deficient Pol γ in cardiac tissue caused a greater than 23-fold increase in mtDNA point mutations and detectable levels of large mtDNA deletions.

    “In mice, transgenic overexpression of exonuclease-deficient Pol γ in cardiac tissue caused a greater than 23-fold increase in mtDNA point mutations and detectable levels of large mtDNA deletions (Zhang et al., 2000).”

Cites

Flagged first, then by citations

Cited by

Sorted by citations

Authors
Zhang, D., Mott, J. L., Chang, S.-W., Denniger, G., Feng, Z., & Zassenhaus, H. P.
Affiliations
Saint Louis University (US)
Corresponding author
Zassenhaus, Hans Peter
Venue
Genomics
Publisher
Elsevier BV
Published
2000-10
Volume
69
Issue
2
Pages
151-161
ISSN
0888-7543 (ISSN-L)
OpenAlex
W2005953994
Cited by
124
References
44
Citations by year
2026: 2 · 2025: 4 · 2024: 1 · 2022: 2 · 2021: 1 · 2020: 4 · 2019: 2 · 2018: 1 · 2017: 4 · 2016: 6 · 2015: 6 · 2014: 4 · 2013: 6 · 2012: 3
FWCI
2.65
Type
journal article
Language
en
Open access
closed
Locations
  • Genomics (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Institutes of Health
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
Keywords
transgenic mice, alpha-myosin heavy chain promoter, cardiomyopathy, mitochondrial DNA deletions, direct repeats, tissue-specific mutagenesis, heart
MeSH terms
DNA Polymerase gamma, Animals, DNA-Directed DNA Polymerase, DNA, Mitochondrial, Genes, Dominant, Heart, Mice, Transgenic, Mitochondria, Heart, Mutation, Organ Specificity, Mutagenesis, Gene Expression Profiling, Mice

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review