ArticlePLoS genetics2020
Genetic compensation prevents myopathy and heart failure in an in vivo model of Bag3 deficiency.
Article in PLoS genetics, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 32 citations in OpenAlex.
- Klhl41b orchestrates sarcomere assembly and growth to drive skeletal muscle hypertrophy in vivo.Skeletal muscle · 2026Article
- Genetic Variants Associated with Life Expectancy in Patients with Chagas Disease.Medical sciences (Basel, Switzerland) · 2026Article
- One BAG Does Not Fit All: Differences and Similarities of BAG Family Members in Mediating Central Nervous System Homeostasis.Biological psychiatry · 2025Review
- Tafazzin-deficient zebrafish display mitochondrial dysfunction, neutropenia, and metabolic defects without myopathy.Scientific reports · 2025Article
- Article
- Smarce1 fine-tunes cardiomyocyte proliferation in the embryonic zebrafish heart.Frontiers in cell and developmental biology · 2025Article
- Prevalence of and gene regulatory constraints on transcriptional adaptation in single cells.Genome biology · 2024Article
- Risk Assessment and Personalized Treatment Options in Inherited Dilated Cardiomyopathies: A Narrative Review.Biomedicines · 2024Review
- A decrease in Fkbp52 alters autophagosome maturation and A152T-tau clearanceFrontiers in cellular neuroscience · 2024Article
- CRISPR/Cas9-mediated nexilin deficiency interferes with cardiac contractile function in zebrafish in vivo.Scientific reports · 2023Article
- Prevalence of and gene regulatory constraints on transcriptional adaptation in single cells.bioRxiv : the preprint server for biology · 2023Article
- Integrated Comparative Transcriptome and circRNA-lncRNA-miRNA-mRNA ceRNA Regulatory Network Analyses Identify Molecular Mechanisms Associated with Intramuscular Fat Content in Beef Cattle.Animals : an open access journal from MDPI · 2023Article
- NRAP reduction rescues sarcomere defects in nebulin-related nemaline myopathy.Human molecular genetics · 2023Article
- Comprehensive review on gene mutations contributing to dilated cardiomyopathy.Frontiers in cardiovascular medicine · 2023Review
- CRISPR/Cas9-Mediated Constitutive Loss of VCP (Valosin-Containing Protein) Impairs Proteostasis and Leads to Defective Striated Muscle Structure and Function In Vivo.International journal of molecular sciences · 2022Article
- CRISPR screens for lipid regulators reveal a role for ER-bound SNX13 in lysosomal cholesterol export.The Journal of cell biology · 2022Article
- HLH-1 Modulates Muscle Proteostasis DuringFrontiers in cell and developmental biology · 2022Article
- Role of BAG5 in Protein Quality Control: Double-Edged Sword?Frontiers in aging · 2022Review
- Genotype to Phenotype: CRISPR Gene Editing Reveals Genetic Compensation as a Mechanism for Phenotypic Disjunction of Morphants and Mutants.International journal of molecular sciences · 2021Review
- Comprehensive Analysis of N6-Methyladenosine RNA Methylation Regulators Expression Identify Distinct Molecular Subtypes of Myocardial Infarction.Frontiers in cell and developmental biology · 2021Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mutations in the molecular co-chaperone Bcl2-associated athanogene 3 (BAG3) are found to cause dilated cardiomyopathy (DCM), resulting in systolic dysfunction and heart failure, as well as myofibrillar myopathy (MFM), which is characterized by protein aggregation and myofibrillar disintegration in skeletal muscle cells. Here, we generated a CRISPR/Cas9-induced Bag3 knockout zebrafish line and found the complete preservation of heart and skeletal muscle structure and function during embryonic development, in contrast to morpholino-mediated knockdown of Bag3. Intriguingly, genetic compensation, a process of transcriptional adaptation which acts independent of protein feedback loops, was found to prevent heart and skeletal muscle damage in our Bag3 knockout model. Proteomic profiling and quantitative real-time PCR analyses identified Bag2, another member of the Bag protein family, significantly upregulated on a transcript and protein level in bag3-/- mutants. This implied that the decay of bag3 mutant mRNA in homozygous bag3-/- embryos caused the transcriptional upregulation of bag2 expression. We further demonstrated that morpholino-mediated knockdown of Bag2 in bag3-/- embryos evoked severe functional and structural heart and skeletal muscle defects, which are similar to Bag3 morphants. However, Bag2 knockdown in bag3+/+ or bag3+/- embryos did not result in (cardio-)myopathy. Finally, we found that inhibition of the nonsense-mediated mRNA decay (NMD) machinery by knockdown of upf1, an essential NMD factor, caused severe heart and skeletal muscle defects in bag3-/- mutants due to the blockade of transcriptional adaptation of bag2 expression. Our findings provide evidence that genetic compensation might vitally influence the penetrance of disease-causing bag3 mutations in vivo.
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