ArticleHuman molecular genetics2005
Mdm muscular dystrophy: interactions with calpain 3 and a novel functional role for titin's N2A domain.
Article in Human molecular genetics, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 56 citations in OpenAlex.
- CaMKIIβ Signaling drives expression of metabolic and stress response genes in skeletal muscle, and its loss contributes to the LGMDR1 phenotype.Human molecular genetics · 2026Article
- Oligomer-dependent and oligomer-independent pathogenesis of muscular dystrophy-associated mutations within the penta-EF-hand domain of calpain-3.The Journal of biological chemistry · 2026Article
- Mending the Achilles heels of titin in cardiac and musculoskeletal disease.Biophysical reviews · 2026Review
- Titin Cardiomyopathy, Emerging Evidence: More Than A Big Heart.Current cardiology reports · 2025Review
- Transcriptomic profiles of muscular dystrophy with myositis (mdm) in extensor digitorum longus, psoas, and soleus muscles from mice.BMC genomics · 2022Article
- Contributions of Titin and Collagen to Passive Stress in Muscles fromInternational journal of molecular sciences · 2022Article
- Protein Quality Control at the Sarcomere: Titin Protection and Turnover and Implications for Disease Development.Frontiers in physiology · 2022Review
- Protein Unfolding: Denaturant vs. Force.Biomedicines · 2021Article
- Titin N2A Domain and Its Interactions at the Sarcomere.International journal of molecular sciences · 2021Review
- The N2A region of titin has a unique structural configuration.The Journal of general physiology · 2021Article
- N2A Titin: Signaling Hub and Mechanical Switch in Skeletal Muscle.International journal of molecular sciences · 2020Review
- Differences in stability and calcium sensitivity of the Ig domains in titin's N2A region.Protein science : a publication of the Protein Society · 2020Article
- Homozygous missense variant in the TTN gene causing autosomal recessive limb-girdle muscular dystrophy type 10.BMC medical genetics · 2019Article
- The effects of a skeletal muscle titin mutation on walking in mice.Journal of comparative physiology. A, Neuroethology, sensory, neural, and behavioral physiology · 2017Article
- Autolytic activation of calpain 3 proteinase is facilitated by calmodulin protein.The Journal of biological chemistry · 2015Article
- Animal models of muscular dystrophy.Progress in molecular biology and translational science · 2012Review
- Pathogenity of some limb girdle muscular dystrophy mutations can result from reduced anchorage to myofibrils and altered stability of calpain 3.Human molecular genetics · 2011Article
- Skeletal muscle-specific calpain is an intracellular Na+-dependent protease.The Journal of biological chemistry · 2010Article
- Down-regulation of MyoD by calpain 3 promotes generation of reserve cells in C2C12 myoblasts.The Journal of biological chemistry · 2010Article
- Calcium-dependent plasma membrane repair requires m- or mu-calpain, but not calpain-3, the proteasome, or caspases.Biochimica et biophysica acta · 2009Article
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Human tibial muscular dystrophy and limb-girdle muscular dystrophy 2J are caused by mutations in the giant sarcomeric protein titin (TTN) adjacent to a binding site for the muscle-specific protease calpain 3 (CAPN3). Muscular dystrophy with myositis (mdm) is a recessive mouse mutation with severe and progressive muscular degeneration caused by a deletion in the N2A domain of titin (TTN-N2ADelta83), disrupting a putative binding site for CAPN3. To determine whether the muscular dystrophy in mutant mdm mice is caused by misregulation of CAPN3 activity, genetic crosses with CAPN3 overexpressing transgenic (C3Tg) and CAPN3 knockout (C3KO) mice were generated. Here, we report that overexpression of CAPN3 exacerbates the mdm disease, leading to a shorter life span and more severe muscular dystrophy. However, in a direct genetic test of CAPN3's role as a mediator of mdm pathology, C3KO;mdm double mutant mice showed no change in the progression or severity of disease indicating that aberrant CAPN3 activity is not a primary mechanism in this disease. To determine whether we could detect a functional deficit in titin in a non-disease state, we examined the treadmill locomotion of heterozygous +/mdm mice and detected a significant increase in stride time with a concomitant increase in stance time. Interestingly, these altered gait parameters were completely corrected by CAPN3 overexpression in transgenic C3Tg;+/mdm mice, supporting a CAPN3-dependent role for the N2A domain of TTN in the dynamics of muscle contraction.
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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.