John McAnally
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View article: Precise gene editing of pathogenic Lamin A mutations corrects cardiac disease
Precise gene editing of pathogenic Lamin A mutations corrects cardiac disease Open
Mutations in the Lamin A ( LMNA ) gene, which encodes the Lamin A and C proteins, cause severe human diseases collectively known as laminopathies. These conditions are often devastating and lack effective therapies. In this study, we devel…
View article: A mechanistic basis of fast myofiber vulnerability to neuromuscular diseases
A mechanistic basis of fast myofiber vulnerability to neuromuscular diseases Open
Neuromuscular diseases such as amyotrophic lateral sclerosis and sarcopenia cause muscle atrophy, which preferentially affects fast-twitch glycolytic myofibers. The mechanisms underlying the susceptibility of fast myofibers to disease rema…
View article: Genomic Editing of a Pathogenic Sequence Variant in <i>ACTA2</i> Rescues Multisystemic Smooth Muscle Dysfunction Syndrome in Mice
Genomic Editing of a Pathogenic Sequence Variant in <i>ACTA2</i> Rescues Multisystemic Smooth Muscle Dysfunction Syndrome in Mice Open
BACKGROUND: Vascular smooth muscle cells (SMCs), the predominant cell type in the aortic wall, play a crucial role in maintaining aortic integrity, blood pressure, and cardiovascular function. Vascular SMC contractility and function depend…
View article: RBPMS regulates cardiomyocyte contraction and cardiac function through RNA alternative splicing
RBPMS regulates cardiomyocyte contraction and cardiac function through RNA alternative splicing Open
Aims RNA binding proteins play essential roles in mediating RNA splicing and are key post-transcriptional regulators in the heart. Our recent study demonstrated that RBPMS (RNA binding protein with multiple splicing) is crucial for cardiac…
View article: CRISPR-Cas9 base editing of pathogenic CaMKIIδ improves cardiac function in a humanized mouse model
CRISPR-Cas9 base editing of pathogenic CaMKIIδ improves cardiac function in a humanized mouse model Open
Cardiovascular diseases are the most common cause of worldwide morbidity and mortality, highlighting the necessity for advanced therapeutic strategies. Ca2+/calmodulin-dependent protein kinase IIδ (CaMKIIδ) is a prominent inducer of variou…
View article: Elimination of CaMKIIδ Autophosphorylation by CRISPR-Cas9 Base Editing Improves Survival and Cardiac Function in Heart Failure in Mice
Elimination of CaMKIIδ Autophosphorylation by CRISPR-Cas9 Base Editing Improves Survival and Cardiac Function in Heart Failure in Mice Open
BACKGROUND: Cardiovascular diseases are the main cause of worldwide morbidity and mortality, highlighting the need for new therapeutic strategies. Autophosphorylation and subsequent overactivation of the cardiac stress-responsive enzyme Ca…
View article: Net39 protects muscle nuclei from mechanical stress during the pathogenesis of Emery-Dreifuss muscular dystrophy
Net39 protects muscle nuclei from mechanical stress during the pathogenesis of Emery-Dreifuss muscular dystrophy Open
Mutations in genes encoding nuclear envelope proteins lead to diseases known as nuclear envelopathies, characterized by skeletal muscle and heart abnormalities, such as Emery-Dreifuss muscular dystrophy (EDMD). The tissue-specific role of …
View article: Precise genomic editing of pathogenic mutations in <i>RBM20</i> rescues dilated cardiomyopathy
Precise genomic editing of pathogenic mutations in <i>RBM20</i> rescues dilated cardiomyopathy Open
Mutations in RNA binding motif protein 20 ( RBM20 ) are a common cause of familial dilated cardiomyopathy (DCM). Many RBM20 mutations cluster within an arginine/serine-rich (RS-rich) domain, which mediates nuclear localization. These mutat…
View article: Loss of function of the nuclear envelope protein LEMD2 causes DNA damage–dependent cardiomyopathy
Loss of function of the nuclear envelope protein LEMD2 causes DNA damage–dependent cardiomyopathy Open
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 card…
View article: A humanized knockin mouse model of Duchenne muscular dystrophy and its correction by CRISPR-Cas9 therapeutic gene editing
A humanized knockin mouse model of Duchenne muscular dystrophy and its correction by CRISPR-Cas9 therapeutic gene editing Open
Duchenne muscular dystrophy (DMD) is a lethal neuromuscular disease caused by mutations in the X-linked dystrophin (DMD) gene. Exon deletions flanking exon 51, which disrupt the dystrophin open reading frame (ORF), represent one of the mos…
View article: Impaired activity of the fusogenic micropeptide Myomixer causes myopathy resembling Carey-Fineman-Ziter syndrome
Impaired activity of the fusogenic micropeptide Myomixer causes myopathy resembling Carey-Fineman-Ziter syndrome Open
Skeletal muscle fibers contain hundreds of nuclei, which increase the overall transcriptional activity of the tissue and perform specialized functions. Multinucleation occurs through myoblast fusion, mediated by the muscle fusogens Myomake…
View article: Matricellular Protein Cilp1 Promotes Myocardial Fibrosis in Response to Myocardial Infarction
Matricellular Protein Cilp1 Promotes Myocardial Fibrosis in Response to Myocardial Infarction Open
Rationale: Cilp1 (cartilage intermediate layer protein 1) is a secreted extracellular matrix protein normally associated with bone and cartilage development. Its function and mechanism of action in adult heart disease remain elusive. Objec…
View article: Regulation of cold-induced thermogenesis by the RNA binding protein FAM195A
Regulation of cold-induced thermogenesis by the RNA binding protein FAM195A Open
Significance Activation of brown adipose tissue offers a strategy for enhancing energy expenditure to counteract obesity and other metabolic disorders. The discovery of novel factors regulating brown adipose tissue function has implication…
View article: A myocardin-adjacent lncRNA balances SRF-dependent gene transcription in the heart
A myocardin-adjacent lncRNA balances SRF-dependent gene transcription in the heart Open
Myocardin, a potent coactivator of serum response factor (SRF), competes with ternary complex factor (TCF) proteins for SRF binding to balance opposing mitogenic and myogenic gene programs in cardiac and smooth muscle. Here we identify a c…
View article: Degenerative and regenerative pathways underlying Duchenne muscular dystrophy revealed by single-nucleus RNA sequencing
Degenerative and regenerative pathways underlying Duchenne muscular dystrophy revealed by single-nucleus RNA sequencing Open
Significance Skeletal muscle is composed of multinucleated myofibers that are essential for movement and metabolism. Duchenne muscular dystrophy (DMD) is a devastating disease that is caused by the lack of the dystrophin protein, which mai…
View article: CRISPR-Mediated Activation of Endogenous Gene Expression in the Postnatal Heart
CRISPR-Mediated Activation of Endogenous Gene Expression in the Postnatal Heart Open
Rationale: Genome editing by CRISPR (clustered regularly interspaced short palindromic repeats)/Cas9 is evolving rapidly. Recently, second-generation CRISPR/Cas9 activation systems based on nuclease inactive dead (d)Cas9 fused to transcrip…
View article: CRISPR-Cas9 corrects Duchenne muscular dystrophy exon 44 deletion mutations in mice and human cells
CRISPR-Cas9 corrects Duchenne muscular dystrophy exon 44 deletion mutations in mice and human cells Open
A mouse model with a common human DMD mutation was created and corrected by CRISPR-Cas9 gene editing.
View article: MOXI Is a Mitochondrial Micropeptide That Enhances Fatty Acid β-Oxidation
MOXI Is a Mitochondrial Micropeptide That Enhances Fatty Acid β-Oxidation Open
Micropeptide regulator of β-oxidation (MOXI) is a conserved muscle-enriched protein encoded by an RNA transcript misannotated as non-coding. MOXI localizes to the inner mitochondrial membrane where it associates with the mitochondrial trif…
View article: Fusogenic micropeptide Myomixer is essential for satellite cell fusion and muscle regeneration
Fusogenic micropeptide Myomixer is essential for satellite cell fusion and muscle regeneration Open
Significance Skeletal muscle damaged by injury or disease can regenerate new muscle fibers. The regenerative properties of skeletal muscle involve fusion of activated muscle stem cells (satellite cells). We recently discovered Myomixer, a …
View article: Single-cut genome editing restores dystrophin expression in a new mouse model of muscular dystrophy
Single-cut genome editing restores dystrophin expression in a new mouse model of muscular dystrophy Open
Single-cut correction of a dystrophin gene mutation with CRISPR/Cas9 restored dystrophin expression in skeletal and cardiac muscles in a mouse model of Duchenne muscular dystrophy.
View article: Deficiency in Kelch protein Klhl31 causes congenital myopathy in mice
Deficiency in Kelch protein Klhl31 causes congenital myopathy in mice Open
Maintenance of muscle structure and function depends on the precise organization of contractile proteins into sarcomeres and coupling of the contractile apparatus to the sarcoplasmic reticulum (SR), which serves as the reservoir for calciu…
View article: CRISPR-Cpf1 correction of muscular dystrophy mutations in human cardiomyocytes and mice
CRISPR-Cpf1 correction of muscular dystrophy mutations in human cardiomyocytes and mice Open
CRISPR-Cpf1–mediated correction of Duchenne muscular dystrophy mutations in human cells and a mouse model.
View article: Control of muscle formation by the fusogenic micropeptide myomixer
Control of muscle formation by the fusogenic micropeptide myomixer Open
Micromanaging muscle cell fusion Adult skeletal muscles are characterized by long, multinucleated cells called myofibers. Myofibers form when muscle precursor cells, or myoblasts, differentiate and fuse together during embryogenesis. The f…