ArticleProceedings of the National Academy of Sciences of the United States of America2015
Consequences of zygote injection and germline transfer of mutant human mitochondrial DNA in mice.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
25 citing papers in PubMed, 42 citations in OpenAlex.
- Mitochondrial genome microhomology-mediated editing by donor DNA delivery into mitochondria in human cells.Molecular therapy. Nucleic acids · 2026Article
- Oxidative stress imbalance and cellular damage mediated by the ND4 G11778A mutation.Scientific reports · 2026Article
- Advances in gene therapy for mitochondrial genetic disorders: current status and clinical implementation challenges.Journal of translational medicine · 2025Review
- Mitochondria-targeted gene delivery using fluorinated lipid nanoparticles to alleviate Leber's hereditary optic neuropathy.Nature communications · 2025Article
- Preclinical Assessment of Mitochondrial-Targeted ND4 Gene Therapy for Leber Hereditary Optic Neuropathy.Investigative ophthalmology & visual science · 2025Article
- Development of Two In Vitro ND1-LHON Models for Evaluating Gene Therapy Efficacy.Investigative ophthalmology & visual science · 2025Article
- Serum neuronal, glial and mitochondrial markers in autosomal dominant optic atrophy and Leber hereditary optic neuropathy.Brain communications · 2025Article
- Hypoxia-mediated rescue of retinal ganglion cells deficient in mitochondrial complex I is independent of the hypoxia-inducible factor pathway.Scientific reports · 2024Article
- Opa1 and MT-Nd6 mutations induce early mitochondrial changes in the retina and prelaminar optic nerve of hereditary optic neuropathy mouse models.Brain communications · 2024Article
- Mitochondrially Targeted Gene Therapy Rescues Visual Loss in a Mouse Model of Leber's Hereditary Optic Neuropathy.International journal of molecular sciences · 2023Article
- Continuous Hypoxia Reduces Retinal Ganglion Cell Degeneration in a Mouse Model of Mitochondrial Optic Neuropathy.Investigative ophthalmology & visual science · 2022Article
- AAV-vector based gene therapy for mitochondrial disease: progress and future perspectives.Orphanet journal of rare diseases · 2022Review
- Gene therapy restores mitochondrial function and protects retinal ganglion cells in optic neuropathy induced by a mito-targeted mutant ND1 gene.Gene therapy · 2022Article
- Adeno-Associated Viruses for Modeling Neurological Diseases in Animals: Achievements and Prospects.Biomedicines · 2022Review
- Advances in Genome Editing and Application to the Generation of Genetically Modified Rat Models.Frontiers in genetics · 2021Review
- Allotopic Expression of ATP6 in Mouse as a Transgenic Model of Mitochondrial Disease.Methods in molecular biology (Clifton, N.J.) · 2021Article
- Review
- Progressive optic atrophy in a retinal ganglion cell-specific mouse model of complex I deficiency.Scientific reports · 2020Article
- Mitochondrial Transfer of the Mutant HumanTranslational vision science & technology · 2020Article
- XIAP Protects Retinal Ganglion Cells in the Mutant ND4 Mouse Model of Leber Hereditary Optic Neuropathy.Investigative ophthalmology & visual science · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
Considerable evidence supports mutations in mitochondrial genes as the cause of maternally inherited diseases affecting tissues that rely primarily on oxidative energy metabolism, usually the nervous system, the heart, and skeletal muscles. Mitochondrial diseases are diverse, and animal models currently are limited. Here we introduced a mutant human mitochondrial gene responsible for Leber hereditary optic neuropathy (LHON) into the mouse germ line using fluorescence imaging for tissue-specific enrichment in the target retinal ganglion cells. A mitochondria-targeted adeno-associated virus (MTS-AAV) containing the mutant human NADH ubiquinone oxidoreductase subunit 4 (ND4) gene followed by mitochondrial-encoded mCherry was microinjected into zygotes. Female founders with mCherry fluorescence on ophthalmoscopy were backcrossed with normal males for eight generations. Mutant human ND4 DNA was 20% of mouse ND4 and did not integrate into the host genome. Translated human ND4 protein assembled into host respiratory complexes, decreasing respiratory chain function and increasing oxidative stress. Swelling of the optic nerve head was followed by progressive demise of ganglion cells and their axons, the hallmarks of human LHON. Early visual loss that began at 3 mo and progressed to blindness 8 mo after birth was reversed by intraocular injection of MTS-AAV expressing wild-type human ND4. The technology of introducing human mitochondrial genes into the mouse germ line has never been described, to our knowledge, and has implications not only for creating animal models recapitulating the counterpart human disorder but more importantly for reversing the adverse effects of the mutant gene using gene therapy to deliver the wild-type allele.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.