ArticleThe Journal of clinical investigation2022
Loss of function of the nuclear envelope protein LEMD2 causes DNA damage-dependent cardiomyopathy.
Article in The Journal of clinical investigation, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 23 citations in OpenAlex.
- Nuclear mechanobiology: a brief history and five unresolved questions.Nucleus (Austin, Tex.) · 2026Article
- DNA damage and repair in cardiomyopathy: mechanisms and therapeutic opportunities.American journal of physiology. Heart and circulatory physiology · 2026Review
- LEM-Domain-Containing Inner Nuclear Membrane Proteins: Emerging Regulators of Intranuclear Signaling.International journal of molecular sciences · 2026Review
- The Pathogenic Role of the DNA Double-Stranded Breaks in Hereditary Cardiomyopathies.Heart failure clinics · 2026Review
- Genetic Animal Models of Cardiovascular Pathologies.Biomedicines · 2025Review
- Review
- Transcriptomic analysis of Paraoxonase 1 expression in hepatocellular carcinoma and its potential impact on tumor immunity.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2025Article
- Circadian system and aging: where both times interact.Frontiers in aging · 2025Review
- A novel role for CSA in the regulation of nuclear envelope integrity: uncovering a non-canonical function.Life science alliance · 2024Article
- The role of kinesin superfamily proteins in hepatocellular carcinoma.Medical oncology (Northwood, London, England) · 2024Review
- Urolithin C suppresses colorectal cancer progression via the AKT/mTOR pathway.Journal of natural medicines · 2024Article
- LEMD2-associated progeroid syndrome: Expanding the phenotype of the nuclear envelopathy caused by a defect in LEMD2 gene.Aging cell · 2024Article
- The expression and role of the Lem-D proteins Ankle2, Emerin, Lemd2, and TMPO in triple-negative breast cancer cell growth.Frontiers in oncology · 2024Article
- Epigenetic silencing ofEpigenomics · 2024Article
- Nuclear envelope assembly relies on CHMP-7 in the absence of BAF-LEM-mediated hole closure.Journal of cell science · 2023Article
- Identification of acetyl-CoA carboxylase alpha as a prognostic and targeted candidate for hepatocellular carcinoma.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2023Article
- Long-Term Transcriptomic Changes and Cardiomyocyte Hyperpolyploidy after Lactose Intolerance in Neonatal Rats.International journal of molecular sciences · 2023Article
- Rodent Models of Dilated Cardiomyopathy and Heart Failure for Translational Investigations and Therapeutic Discovery.International journal of molecular sciences · 2023Review
- Nuclear mechanosignaling in striated muscle diseases.Frontiers in physiology · 2023Review
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
Mutations in nuclear envelope proteins (NEPs) cause devastating genetic diseases, known as envelopathies, that primarily affect the heart and skeletal muscle. A mutation in the NEP LEM domain-containing protein 2 (LEMD2) causes severe cardiomyopathy in humans. However, the roles of LEMD2 in the heart and the pathological mechanisms responsible for its association with cardiac disease are unknown. We generated knockin (KI) mice carrying the human c.T38>G Lemd2 mutation, which causes a missense amino acid exchange (p.L13>R) in the LEM domain of the protein. These mice represent a preclinical model that phenocopies the human disease, as they developed severe dilated cardiomyopathy and cardiac fibrosis leading to premature death. At the cellular level, KI/KI cardiomyocytes exhibited disorganization of the transcriptionally silent heterochromatin associated with the nuclear envelope. Moreover, mice with cardiac-specific deletion of Lemd2 also died shortly after birth due to heart abnormalities. Cardiomyocytes lacking Lemd2 displayed nuclear envelope deformations and extensive DNA damage and apoptosis linked to p53 activation. Importantly, cardiomyocyte-specific Lemd2 gene therapy via adeno-associated virus rescued cardiac function in KI/KI mice. Together, our results reveal the essentiality of LEMD2 for genome stability and cardiac function and unveil its mechanistic association with human disease.
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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.