Junction Of Muscle Research Articles

Anti-LRP4 autoantibodies in AChR- and MuSK-antibody-negative myasthenia gravis

Myasthenia gravis (MG) is an autoimmune disorder characterized by a defect in synaptic transmission at the neuromuscular junction causing fluctuating muscle weakness with a decremental response to repetitive nerve stimulation or altered jitter in single-fiber electromyography (EMG). Approximately 80% of all myasthenia gravis patients have autoantibodies against the nicotinic acetylcholine receptor in their serum. Autoantibodies against the tyrosine kinase muscle-specific kinase (MuSK) are responsible for 5-10% of all myasthenia gravis cases. The autoimmune target in the remaining cases is unknown. Recently, low-density lipoprotein receptor-related protein (LRP4) has been identified as the agrin receptor. LRP4 interacts with agrin, and the binding of agrin activates MuSK, which leads to the formation of most if not all postsynaptic specializations, including aggregates containing acetylcholine receptors (AChRs) in the junctional plasma membrane. In the present study we tested if autoantibodies against LRP4 are detectable in patients with myasthenia gravis. To this end we analyzed 13 sera from patients with generalized myasthenia gravis but without antibodies against AChR or MuSK. The results showed that 12 out of 13 antisera from double-seronegative MG patients bound to proteins concentrated at the neuromuscular junction of adult mouse skeletal muscle and that approximately 50% of the tested sera specifically bound to HEK293 cells transfected with human LRP4. Moreover, 4 out of these 13 sera inhibited agrin-induced aggregation of AChRs in cultured myotubes by more than 50%, suggesting a pathogenic role regarding the dysfunction of the neuromuscular endplate. These results indicate that LRP4 is a novel target for autoantibodies and is a diagnostic marker in seronegative MG patients.

A method to characterize in vivo tendon force–strain relationship by combining ultrasonography, motion capture and loading rates

The ultrasonography contributes to investigate in vivo tendon force–strain relationship during isometric contraction. In previous studies, different methods are available to estimate the tendon strain, using different loading rates and models to fit the tendon force–strain relationship. This study was aimed to propose a standard method to characterize the in vivo tendon force–strain relationship. We investigated the influence on the force–strain relationship for medialis gastrocnemius (MG) of (1) one method which takes into account probe and joint movements to estimate the instantaneous tendon length, (2) models used to fit the force–strain relationship for uniaxial test (polynomial vs. Ogden), and (3) the loading rate on tendon strain. Subjects performed ramp-up contraction during isometric contractions at two different target speeds: 1.5s and minimal time with ultrasound probe fixed over the muscle–tendon junction of the MG muscle. The used method requires three markers on ultrasound probe and a marker on calcaneum to take into account all movements, and was compared to the strain estimated using ultrasound images only. The method using ultrasound image only overestimated the tendon strain from 40% of maximal force. The polynomial model showed similar fitting results than the Ogden model (R²=0.98). A loading rate effect was found on tendon strain, showing a higher strain when loading rate decreases. The characterization of tendon force–strain relationship needs to be standardized by taking into account all movements to estimate tendon strain and controlling the loading rate. The polynomial model appears to be appropriate to represent the tendon force–strain relationship.

Ressalto no canto posteromedial do joelho relacionado ao músculo sartório

As causas da síndrome de ressalto no joelho relatadas com maior frequência são relacionadas a anormalidades meniscais, ao tendão do músculo bíceps femoral e aos tendões grácil e semitendíneo. Neste trabalho é descrito um caso de ressalto no canto posteromedial relacionado à junção miotendínea do músculo sartório em um paciente do sexo masculino, de 58 anos de idade, com hiperextensão do joelho.

Do palisade endings in extraocular muscles arise from neurons in the motor nuclei?

The purpose of this study was to localize the cell bodies of palisade endings that are associated with the myotendinous junctions of the extraocular muscles. Rhesus monkeys received tract-tracer injections (tetramethylrhodamine dextran [TMR-DA] or choleratoxin subunit B [CTB]) into the oculomotor and trochlear nuclei, which contain the motoneurons of extraocular muscles. All extraocular muscles were processed for the combined immunocytochemical detection of the tracer and SNAP-25 or synaptophysin for the visualization of the complete muscle innervation. In all muscles--except the lateral rectus--en plaque and en grappe motor endings, but also palisade endings, were anterogradely labeled. In addition a few tracer-labeled tendon organs were found. One group of tracer-negative nerve fibers was identified as thin tyrosine hydroxylase-positive sympathetic fibers, and a second less numerous group of tracer-negative fibers may originate from the trigeminal ganglia. No cellular or terminal tracer labeling was present within the mesencephalic trigeminal nucleus or the trigeminal ganglia. These results confirm those of earlier studies and furthermore suggest that the somata of palisade endings are located close to the extraocular motor nuclei--in this case, probably within the C and S groups around the periphery of the oculomotor nucleus. The multiple en grappe endings have also been shown to arise from these cells groups, but it is not possible to distinguish different populations in these experiments.

Differential and restricted expression of novel collagen VI chains in mouse

Recently, three novel collagen VI chains, α4, α5 and α6, were identified. These are thought to substitute for the collagen VI α3 chain, probably forming α1α2α4, α1α2α5 or α1α2α6 heterotrimers. The expression pattern of the novel chains is so far largely unknown. In the present study, we compared the tissue distribution of the novel collagen VI chains in mouse with that of the α3 chain by immunohistochemistry, immunoelectron microscopy and immunoblots. In contrast to the widely expressed α3 chain, the novel chains show a highly differential, restricted and often complementary expression. The α4 chain is strongly expressed in the intestinal smooth muscle, surrounding the follicles in ovary, and in testis. The α5 chain is present in perimysium and at the neuromuscular junctions in skeletal muscle, in skin, in the kidney glomerulus, in the interfollicular stroma in ovary and in the tunica albuginea of testis. The α6 chain is most abundant in the endomysium and perimysium of skeletal muscle and in myocard. Immunoelectron microscopy of skeletal muscle localized the α6 chain to the reticular lamina of muscle fibers. The highly differential and restricted expression points to the possibility of tissue-specific roles of the novel chains in collagen VI assembly and function.

The Interaction between Tropomyosin-Related Kinase B Receptors and Presynaptic Muscarinic Receptors Modulates Transmitter Release in Adult Rodent Motor Nerve Terminals

The neurotrophin brain-derived neurotrophic factor (BDNF), neurotrophin-4 (NT-4) and the receptors tropomyosin-related kinase B (trkB) and p75(NTR) are present in the nerve terminals on the neuromuscular junctions (NMJs) of the levator auris longus muscle of the adult mouse. Exogenously added BDNF or NT-4 increased evoked ACh release after 3 h. This presynaptic effect (the size of the spontaneous potentials is not affected) is specific because it is not produced by neurotrophin-3 (NT-3) and is prevented by preincubation with trkB-IgG chimera or by pharmacological block of trkB [K-252a (C₂₇H₂₁N₃O₅)] or p75(NTR) [Pep5 (C₈₆H₁₁₁N₂₅O₁₉S₂] signaling. The effect of BDNF depends on the M₁ and M₂ muscarinic acetylcholine autoreceptors (mAChRs) because it is prevented by atropine, pirenzepine and methoctramine. We found that K-252a incubation reduces ACh release (~50%) in a short time (1 h), but the p75(NTR) signaling inhibitor Pep5 does not have this effect. The specificity of the K-252a blocking effect on trkB was confirmed with the anti-trkB antibody 47/trkB, which reduces evoked ACh release, like K-252a, whereas the nonpermeant tyrosine kinase blocker K-252b does not. Neither does incubation with the fusion protein trkB-IgG (to chelate endogenous BDNF/NT-4), anti-BDNF or anti-NT-4 change ACh release. Thus, the trkB receptor normally seems to be coupled to ACh release when there is no short-term local effect of neurotrophins at the NMJ. The normal function of the mAChR mechanism is a permissive prerequisite for the trkB pathway to couple to ACh release. Reciprocally, the normal function of trkB modulates M₁- and M₂-subtype muscarinic pathways.

Reliability and Relationship Between 2 Measurements of Transversus Abdominis Dimension Taken During an Abdominal Drawing-in Maneuver Using a Novel Approach of Ultrasound Imaging

Reliability study of clinical measurement. The primary purpose was to develop a reliable method for measuring muscle length changes of the transversus abdominis (TrA) during contraction. The secondary purpose was to investigate the relationship between changes in thickness and length (as indicated by the lateral sliding of the anterior muscle-fascia junction) of the TrA muscle during an abdominal drawing-in maneuver. We also provide data on between-day reliability of change in thickness (ΔT) of the TrA. Ultrasound imaging measurements of TrA thickness at rest (Thr) and during maximal contraction (Thm) have been shown to be reliable. However, limited data exist on quantifying changes in TrA length (as indicated by the lateral sliding of the muscle-fascia junction [Δx]) and ΔT during contraction. Eighteen healthy adults (mean ± SD age, 22.6 ± 2.5 years) participated in this study. Brightness mode ultrasound images of the TrA were collected at rest and during an abdominal drawing-in maneuver. Subjects were examined by the same examiner twice within a 48-hour period. ΔT, ΔT/Thr, Thr, Thm, and Δx of the TrA were calculated. Medial-lateral movement of the transducer during measurement was corrected through a custom-written program that used an internal marker created by an echo-absorptive thread attached to the skin. Intraclass correlation coefficients (ICC3,1), within-subject coefficient of variance, and standard error of measurement were calculated. The relationship between ΔT and adjusted Δx of the TrA muscle was investigated. The ICC values for Thr, Thm, and ΔT of the TrA muscle were greater than 0.75, with the exception of the left ΔT (0.62) and left ΔT/Thr (0.49). After adjusting for medial-lateral motion of the transducer, the ICC values of adjusted Δx were above 0.75, and the within-subject coefficient of variance was below 10%. There was no significant correlation between ΔT and adjusted Δx of the TrA. Ultrasound imaging measurements of TrA thickness and length change were shown to be reliable using a novel method to control for medial-lateral transducer motion. Measuring different but unrelated dimensional changes in the TrA might provide further insight as to the function of the TrA.

Synaptic Defects in the Spinal and Neuromuscular Circuitry in a Mouse Model of Spinal Muscular Atrophy

Spinal muscular atrophy (SMA) is a major genetic cause of death in childhood characterized by marked muscle weakness. To investigate mechanisms underlying motor impairment in SMA, we examined the spinal and neuromuscular circuitry governing hindlimb ambulatory behavior in SMA model mice (SMNΔ7). In the neuromuscular circuitry, we found that nearly all neuromuscular junctions (NMJs) in hindlimb muscles of SMNΔ7 mice remained fully innervated at the disease end stage and were capable of eliciting muscle contraction, despite a modest reduction in quantal content. In the spinal circuitry, we observed a ∼28% loss of synapses onto spinal motoneurons in the lateral column of lumbar segments 3–5, and a significant reduction in proprioceptive sensory neurons, which may contribute to the 50% reduction in vesicular glutamate transporter 1(VGLUT1)-positive synapses onto SMNΔ7 motoneurons. In addition, there was an increase in the association of activated microglia with SMNΔ7 motoneurons. Together, our results present a novel concept that synaptic defects occur at multiple levels of the spinal and neuromuscular circuitry in SMNΔ7 mice, and that proprioceptive spinal synapses could be a potential target for SMA therapy.

Neuromuscular pathology in mice lacking alpha-synuclein

This work was undertaken in order to study the possible role of alpha-synuclein in the function of the neuro-muscular junction in skeletal muscles. Repeated stimulation of skeletal muscle motor neurons revealed signs of neuromuscular pathology in alpha-synuclein null mutated (C57Bl/6JOlaHsd) and knockout (B6;129X1-Sncatm1Rosl/J) mice. This stimulation produced repetitive compound muscle action potentials in both lines of alpha-synuclein deficient mice. Muscle strength and muscle coordination during ambulation were unaffected, though motor learning was slower in alpha-synuclein deficient mice in the Rotarod test. We conclude that alpha-synuclein may play a role in acetylcholine compartmentalization at the neuromuscular junction, and in the fine control of activity of skeletal muscles.

Structure/function assessment of synapses at motor nerve terminals

The release of transmitter at neuromuscular junctions (NMJ) of the opener muscle in crayfish is quantal in nature. This NMJ offers the advantage of being able to record quantal events at specific visually identified release sites, thus allowing measurement of the physiological parameters of vesicle release and its response to be directly correlated with synaptic structure. These experiments take advantage of areas between the varicosities on the nerve terminal that we define as "stems." Stems were chosen as the region to study because of their low synaptic output due to fewer synaptic sites. Through 3D reconstruction from hundreds of serial sections, obtained by transmission electron microscopy (TEM), at a site in which focal macropatch recordings were obtained, the number of synapses and AZs are revealed. Thus, physiological profiles with various stimulation conditions can be assessed in regards to direct synaptic structure. Here, we used the properties of the quantal shape to determine if distinct subsets of quantal signatures existed and if differences in the distributions are present depending on the frequency of stimulation. Such a quantal signature could come about by parameters of area, rise time, peak amplitude, latency, and tau decay. In this study, it is shown that even at defined sites on the stem, with few active zones, synaptic transmission is still complex and the quantal responses appear to be variable even for a given synapse over time. In this study, we could not identify a quantal signature for the conditions utilized.

Surgical anatomy of the external branch of the superior laryngeal nerve

The variations in the anatomy of the external branch of the superior laryngeal nerve (EBSLN) are generally classified according to the relationship of the nerve to the superior thyroid artery, or the superior pole of the thyroid. Both artery and superior pole are themselves variable landmarks, and therefore are not consistent between subjects. We sought to examine EBSLN anatomy in relation to alternate, more consistent surgical landmarks. Fifteen hemi-larynges from 20 embalmed human cadavers were dissected anatomically. Each nerve was categorized using established classification systems, and terminal branching patterns were also noted. Nerve location was recorded in relation to three different constant anatomical structures: the laryngeal prominence, midline junction of the cricothyroid muscles and ipsilateral cricothyroid joint. All cadavers were of European descent. The EBSLN had two branches to the cricothyroid muscle in 34% of cases. The EBSLN anatomical types found were mainly Cernea type 1 (80%), with 7% type 2a and 13% type Ni. An EBSLN was more likely to lie in an 'at risk' location if the subject was less than 160 cm tall. The EBSLN entered the crico-thyroid muscle at a median distance of 14 mm lateral from the laryngeal prominence and 8 mm inferiorly. The median distance from the medial-most point of the cricothyroid muscle junction was 14 mm laterally and 14 mm superiorly, and from the cricothyroid joint the entry lay a median distance of 10 mm superiorly and 11 mm medially. The variability of EBSLN anatomy is again evident, as is the need for careful and knowledgeable surgical technique. New surgical landmarks for the relations of the insertion of the EBSLN reveal a deployment range for each, but one of more of these landmarks may prove useful in thyroid surgery.

Disruption of Endothelial Tight Junctions in a Patient with Mitochondrial Encephalomyopathy, Lactic Acidosis and Stroke-Like Episodes (MELAS)

An electron microscopic study revealed disruption of capillary endothelial tight junctions (TJs) in both biopsied muscle, taken at 5 years and 1 month of age, and the autopsied brain, taken at 13 years and 6 months of age, in a patient with mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS) and mitochondrial DNA (mtDNA) point mutation A3243G. This endothelial barrier disruption might result in vasogenic edema and systemic lactic acidosis, possibly the critical pathology of MELAS.

The polyproline site in hinge 2 influences the functional capacity of truncated dystrophins.

Mutations in dystrophin can lead to Duchenne muscular dystrophy or the more mild form of the disease, Becker muscular dystrophy. The hinge 3 region in the rod domain of dystrophin is particularly prone to deletion mutations. In-frame deletions of hinge 3 are predicted to lead to BMD, however the severity of disease can vary considerably. Here we performed extensive structure-function analyses of truncated dystrophins with modified hinges and spectrin-like repeats in mdx mice. We found that the polyproline site in hinge 2 profoundly influences the functional capacity of a microdystrophinΔR4-R23/ΔCT with a large deletion in the hinge 3 region. Inclusion of polyproline in microdystrophinΔR4-R23/ΔCT led to small myofibers (12% smaller than wild-type), Achilles myotendinous disruption, ringed fibers, and aberrant neuromuscular junctions in the mdx gastrocnemius muscles. Replacing hinge 2 of microdystrophinΔR4-R23/ΔCT with hinge 3 significantly improved the functional capacity to prevent muscle degeneration, increase muscle fiber area, and maintain the junctions. We conclude that the rigid α-helical structure of the polyproline site significantly impairs the functional capacity of truncated dystrophins to maintain appropriate connections between the cytoskeleton and extracellular matrix.

Ultrastructure of the myotendinous junction of the medial pterygoid muscle of adult and aged Wistar rats

The myotendon junction (MTJ) is a specialised area into the muscle fibers where the sarcoplasmic membranes connect to the collagen fibers bundles. There are few data about plasticity of the MTJ in aging processes. The aim of this study is to analyse the ultrastructure characteristics of MTJ of medial pterygoid muscle of adult and aged rats. Employing the transmission electron microscopy method, twenty male rats Wistar ( Rattus norvegicus) were divided into two groups: A ( n = 10) with 12 months of age; B ( n = 10) 24 months of age. The animals were anaesthetised with overdose the urethane (3 g/kg, i.p.) and sacrified during the perfusion with modified Karnovsky solution. The specimens were post-fixed in a 1% osmium tetroxide solution, dehydrated in ascending concentration of ethanol and embedded in Spurr resin. The thin sections, of 90 nm thick, were counterstained with uranyl acetate and lead citrate solution, and examined in a Jeol 1010 transmission electron microscope. The fine structure of the MTJ of group A revealed the defined interdigitations and disposed in several levels of deep formations containing the collagen fibers. In the group B, such structures did not observed, detecting the projections irregular in shape, and large of extra matrix with in aspect of remodelling. In conclusion it was possible to identify the plasticity of MTJ in the group B which presented several morphological alterations comparing to the adult animals. These data of group B suggested the occurrence of aging processes in the MTJ in rats.

Identification of the Neuromuscular Junction Transcriptome of Extraocular Muscle by Laser Capture Microdissection

To examine and characterize the profile of genes expressed at the synapses or neuromuscular junctions (NMJs) of extraocular muscles (EOMs) compared with those expressed at the tibialis anterior (TA). Adult rat eyeballs with rectus EOMs attached and TAs were dissected, snap frozen, serially sectioned, and stained for acetylcholinesterase (AChE) to identify the NMJs. Approximately 6000 NMJs for rectus EOM (EOMsyn), 6000 NMJs for TA (TAsyn), equal amounts of NMJ-free fiber regions (EOMfib, TAfib), and underlying myonuclei and RNAs were captured by laser capture microdissection (LCM). RNA was processed for microarray-based expression profiling. Expression profiles and interaction lists were generated for genes differentially expressed at synaptic and nonsynaptic regions of EOM (EOMsyn versus EOMfib) and TA (TAsyn versus TAfib). Profiles were validated by using real-time quantitative polymerase chain reaction (qPCR). The regional transcriptomes associated with NMJs of EOMs and TAs were identified. Two hundred seventy-five genes were preferentially expressed in EOMsyn (compared with EOMfib), 230 in TAsyn (compared with TAfib), and 288 additional transcripts expressed in both synapses. Identified genes included novel genes as well as well-known, evolutionarily conserved synaptic markers (e.g., nicotinic acetylcholine receptor (AChR) alpha (Chrna) and epsilon (Chrne) subunits and nestin (Nes). Transcriptome level differences exist between EOM synaptic regions and TA synaptic regions. The definition of the synaptic transcriptome provides insight into the mechanism of formation and functioning of the unique synapses of EOM and their differential involvement in diseases noted in the EOM allotype.

Hexamethonium produces both twitch and tetanic depression without fade in common African toad (<i>Bufo regularis</i>)

The study was designed to investigate the nature of the cholinoceptors at the sciatic nerve-gastrocnemius muscle junction of the common African toad (Bufo regularis). Using myographic technique, the twitch properties of the sciatic-gastrocnemius muscle preparation of the common African toad was studied. Both the twitch height and peak tetanic height were measured as a percentage of control. Hexamethonium at a concentration of 0.1 mM significantly [P<0.05] reduced the mean twitch height from 2.62 cm to 1.0 cm and mean peak tetanic height from 5.38 cm to 4.32 cm. Hexamethonium, however does not produce tetanic fade at the same concentration. We hypothesized that the cholinoceptors of the neuromuscular junction of the common African toad (Bufo regularis) resemble the developing synapse of African clawed toad (Xenopus laevis) and may contain muscarinic M1 autoreceptors at the pre juntional membrane.

Collapsin Response Mediator Protein 4a (CRMP4a) Is Upregulated in Motoneurons of Mutant SOD1 Mice and Can Trigger Motoneuron Axonal Degeneration and Cell Death

Embryonic motoneurons from mutant SOD1 (mSOD1) mouse models of amyotrophic lateral sclerosis (ALS), but not wild-type motoneurons, can be triggered to die by exposure to nitric oxide (NO), leading to activation of a motoneuron-specific signaling pathway downstream of the death receptor Fas/CD95. To identify effectors of mSOD1-dependent cell death, we performed a proteomic analysis. Treatment of cultured mSOD1 motoneurons with NO led to a 2.5-fold increase in levels of collapsin response mediator protein 4a (CRMP4a). In vivo, the percentage of mSOD1 lumbar motoneurons expressing CRMP4 in mSOD1 mice increased progressively from presymptomatic to early-onset stages, reaching a maximum of 25%. Forced adeno-associated virus (AAV)-mediated expression of CRMP4a in wild-type motoneurons in vitro triggered a process of axonal degeneration and cell death affecting 60% of motoneurons, whereas silencing of CRMP4a in mSOD1 motoneurons protected them from NO-induced death. In vivo, AAV-mediated overexpression of CRMP4a but not CRMP2 led to the death of 30% of the lumbar motoneurons and an 18% increase in denervation of neuromuscular junctions in the gastrocnemius muscle. Our data identify CRMP4a as a potential early effector in the neurodegenerative process in ALS.

Effect of third molar absence on development of masticatory muscles in EL mice

We investigated the effect of the lack of the third molar on synaptogenesis at the neuromuscular junction of masticatory muscles in EL/ Sea (Sea) mice, in which tooth bud of all third molars disappears in the process of development. We analyzed the mRNA expression levels of the nicotinic acetylcholine receptor (nAChR) α , ε, and γ subunits at 3, 6, and 12 weeks of age in the masseter and temporalis muscles of Sea mice, and in the control strain EL/Kwl (Kwl) mice, using real-time PCR. In the Sea, no third molars erupted over the oral mucous membrane during the experimental period. In the Kwl, at 3 weeks of age, no third molars had erupted over the oral mucous membrane, but they partially had emerged over the maxilla and mandible and, after 3 weeks of age, completely erupted over the oral mucous membrane. In the masseter, the expression levels of the α , ε, and γ subunit mRNAs in the Sea mice were 92% ( P < 0.05), 100% ( P < 0.05), and 91% (not significant) higher than in the Kwl mice at 3 weeks of age, but steadily decreased until 12 weeks of age. The expression levels in the Kwl mice were stable throughout the experimental period. In the temporalis and gastrocnemius, there were no significant differences in the expression levels of any of the subunits studied between the Sea and Kwl mice. This result suggests that the difference in the expression of nAChR subunits in the masseter muscle between the Sea and Kwl mice is associated with the eruption of the third molars, and that the absence of the third molars has different effects between the masseter and temporalis.

A New Perspective on Intercalated Disc Organization: Implications for Heart Disease

Adherens junctions and desmosomes are intercellular adhesive junctions and essential for the morphogenesis, differentiation, and maintenance of tissues that are subjected to high mechanical stress, including heart and skin. The different junction complexes are organized at the termini of the cardiomyocyte called the intercalated disc. Disruption of adhesive integrity via mutations in genes encoding desmosomal proteins causes an inherited heart disease, arrhythmogenic right ventricular cardiomyopathy (ARVC). Besides plakoglobin, which is shared by adherens junctions and desmosomes, other desmosomal components, desmoglein-2, desmocollin-2, plakophilin-2, and desmoplakin are also present in ultrastructurally defined fascia adherens junctions of heart muscle, but not other tissues. This mixed-type of junctional structure is termed hybrid adhering junction or area composita. Desmosomal plakophilin-2 directly interacts with adherens junction protein alphaT-catenin, providing a new molecular link between the cadherin-catenin complex and desmosome. The area composita only exists in the cardiac intercalated disc of mammalian species suggesting that it evolved to strengthen mechanical coupling in the heart of higher vertebrates. The cross-talk among different junctions and their implication in the pathogenesis of ARVC are discussed in this review.

C. elegans models of neuromuscular diseases expedite translational research

AbstractThe nematode Caenorhabditis elegans is a genetic model organism and the only animal with a complete nervous system wiring diagram. With only 302 neurons and 95 striated muscle cells, a rich array of mutants with defective locomotion and the facility for individual targeted gene knockdown by RNA interference, it lends itself to the exploration of gene function at nerve muscle junctions. With approximately 60% of human disease genes having a C. elegans homologue, there is growing interest in the deployment of lowcost, high-throughput, drug screens of nematode transgenic and mutant strains mimicking aspects of the pathology of devastating human neuromuscular disorders. Here we explore the contributions already made by C. elegans to our understanding of muscular dystrophies (Duchenne and Becker), spinal muscular atrophy, amyotrophic lateral sclerosis, Friedreich’s ataxia, inclusion body myositis and the prospects for contributions to other neuromuscular disorders. A bottleneck to low-cost, in vivo, large-scale chemical library screening for new candidate therapies has been rapid, automated, behavioural phenotyping. Recent progress in quantifying simple swimming (thrashing) movements is making such screening possible and is expediting the translation of drug candidates towards the clinic.