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PubMed2025

Impact of Muscle Quality on Muscle Strength and Physical Performance Beyond Muscle Mass or Diabetes Status.

BACKGROUND: Muscle quality, represented by myosteatosis, is recognized as an important factor in sarcopenia. In this study, we aimed to determine the associations between myosteatosis, muscle strength and physical performance among the elderly South Korean population. METHODS: We included 1440 participants (mean age 62.7 ± 6.2 years) from the Korean Genome and Epidemiology Study (KoGES). Based on the computed tomography attenuation of mid-thigh imaging, the total muscle area (TMA), normal-attenuation muscle area (NAMA), low-attenuation muscle area (LAMA) and inter-intramuscular adipose tissue (IMAT) and its indices were used to evaluate myosteatosis. Muscle strength was evaluated using hand grip strength, whereas physical performance was evaluated through 4-m gait speed, a 30-s sit-to-stand test and 2-min walking test. RESULTS: Of the 1440 patients, 51.5% were women, and 37.2% had diabetes. With aging, the LAMA index gradually increased, and the NAMA index gradually decreased in both men and women (p for trend < 0.001). The NAMA index was positively associated, whereas the LAMA and IMAT indices were negatively associated with muscle strength and physical performance after adjusting for age and sex. Higher tertiles of the NAMA index were consistently associated with improved physical performance across all appendicular skeletal muscle tertiles. The relationship between the NAMA index or LAMA index and muscle strength and physical performance did not differ according to diabetic status. Regular exercise was associated with a higher NAMA index and a lower LAMA index in the non-diabetic group; however, no significant difference in muscle quality was observed in the diabetic group in relation to exercise. CONCLUSIONS: Reduced myosteatosis was positively associated with greater muscle strength and better physical performance in both men and women, regardless of muscle mass or diabetes status; improving myosteatosis may be a therapeutic target for the prevention of sarcopenia.

Humans↗

PubMed1998

Alterations in information transmission in ensembles of primary muscle spindle afferents after muscle fatigue in heteronymous muscle.

This study showed that fatigue of the ipsilateral medial gastrocnemius muscle caused a clear-cut reduction in the ability of ensembles of primary muscle spindle afferents from the lateral gastrocnemius muscle to discriminate between muscle stretches of varying amplitude. The results were probably caused by reflex-mediated effects from chemosensitive group III and IV afferents onto the gamma-motoneurons projecting to lateral gastrocnemius muscle spindles. The experiments were conducted on seven cats anaesthetized with alpha-chloralose and a total of 41 primary muscle spindle afferents from the lateral gastrocnemius were registered. Afferents were simultaneously recorded in ensembles of three to 10 afferents. A method based on principal component analysis and algorithms for quantification of stimulus discrimination in ensembles of muscle afferents was used prior to, immediately following and five or more minutes after muscle fatigue had been induced to the ipsilateral medial gastrocnemius muscle. It is well established that the primary muscle spindle afferents play an important role in proprioception and kinaesthesia. Therefore the decrease in the accuracy of the information transmitted by ensembles of primary muscle spindle afferents caused by fatigue in an ipsilateral muscle implies concomitant effects on proprioception and kinaesthesia.

Animals↗

PubMed2001

Dystrophin muscle enhancer 1 is implicated in the activation of non-muscle isoforms in the skeletal muscle of patients with X-linked dilated cardiomyopathy.

X-linked dilated cardiomyopathy (XLDC) is a dystrophinopathy characterized by severe cardiomyopathy with no skeletal muscle involvement. Several XLDC patients have been described with mutations that abolish dystrophin muscle (M) isoform expression. The absence of skeletal muscle degeneration normally associated with loss of dystrophin function was shown to be due to increased expression of brain (B) and cerebellar Purkinje (CP) isoforms of the gene exclusively in the skeletal muscle of these patients. This suggested that the B and CP promoters have an inherent capacity to function in skeletal muscle or that they are up-regulated by a skeletal muscle-specific enhancer unaffected by the mutations in these patients. In this work we have analyzed the deletion breakpoints of two XLDC patients with deletions removing the M promoter and exon 1, but not affecting the B and CP promoters. Despite the presence of several muscle-specific regulatory motifs, the B and CP promoters were found to be essentially inactive in muscle cell lines and primary cultures. As dystrophin muscle enhancer 1 (DME1), the only known muscle-specific enhancer within the dystrophin gene, is preserved in these patients, we tested its ability to up-regulate the B and CP promoters in muscle cells. B and CP promoter activity was significantly increased in the presence of DME1, and more importantly, activation was observed exclusively in cells presenting a skeletal muscle phenotype. These results point to a role for DME1 in the induction of B and CP isoform expression in the skeletal muscle of XLDC patients defective for M isoform expression.

3T3 Cells↗

PubMed2002

Serum muscle enzymes, muscle pathology and clinical muscle weakness: correlation in Thai patients with polymyositis/dermatomyositis.

The clinical correlation between serum muscle enzymes, muscle pathology and muscle weakness was studied in 100 Thai patients (22 males and 78 females) with polymyositis (PM) and dermatomyositis (DM). Their mean +/- SD age and duration of disease were 45.0 +/- 13.9 years and 6.3 + 13.4 months, respectively. There was idiopathic PM in 37 cases, idiopathic DM in 13, PM/DM associated with malignancy in 5 and PM associated with connective tissue disease in 45. Serum muscle enzymes including creatine phosphokinase, lactate dehydrogenase and aspartate aminotransferase were elevated in 87 per cent, 92 per cent, and 82 per cent of cases, respectively. Abnormal electromyographic findings that were compatible with inflammatory myopathy were found in 76 per cent of cases. Seventy-seven per cent had an abnormal muscle biopsy that was consistent with polymyositis. There was a significant correlation between serum muscle enzymes and muscle pathology (p < 0.01). The degree of muscle weakness correlated better with the degree of muscle destruction (p = 0.01) than the degree of muscle inflammation (p = 0.03). The erythrocyte sedimentation rate showed no correlation with serum muscle enzymes, muscle pathology or muscle weakness.

Adult↗

PubMed2006

Macrophages promote muscle membrane repair and muscle fibre growth and regeneration during modified muscle loading in mice in vivo.

Muscle injury or modified muscle use can stimulate muscle invasion by leucocytes that have the potential to increase tissue damage or promote tissue growth and repair. In the present investigation, we examined the role of macrophages in muscle injury, repair and regeneration during modified muscle loading. Weight-bearing was removed from the hindlimbs of mice for 10 days followed by reloading through normal ambulation. During the unloading period, soleus muscle fibre cross-section decreased by 38%. Prior to the onset of reloading, mice received a series of intraperitoneal injections of anti-F4/80, which binds a mouse macrophage surface antigen. Although anti-F4/80 injections did not affect macrophage numbers in soleus muscles at 2 days of reloading, macrophages were reduced by 86% at 4 days of reloading. Muscle membrane lysis during the reloading period did not differ at 2 days of reloading between anti-F4/80-treated mice and mice that received isotype control antibody. However, control animals showed large decreases in the number of fibres with membrane lesions at 4 days of reloading, but this membrane repair did not occur in macrophage-depleted mice. Macrophage-depletion also reduced muscle regeneration (indicated by central nucleation) and satellite cell differentiation (indicated by reductions in MyoD-expressing satellite cells) and prevented growth of muscle fibres that normally occurred in control animals between days 2 and 4 of reloading. These findings collectively show that macrophages play a significant role in muscle fibre membrane repair, regeneration and growth during increased muscle use after a period of atrophy.

Animals↗

PubMed2004

Long-term outcome of muscle strength in ulnar and median nerve injury: comparing manual muscle strength testing, grip and pinch strength dynamometers and a new intrinsic muscle strength dynamometer.

OBJECTIVE: To compare the outcome of muscle strength with manual muscle strength testing grip and pinch strength measurements and a dynamometer which allows for measurements of the intrinsic muscles of the hand in isolation (the Rotterdam Intrinsic Hand Myometer, RIHM). METHODS: Thirty-four patients more than 2 years after ulnar and/or median nerve injury. Muscle strength was evaluated using manual muscle strength testing (MMST), grip, pinch and intrinsic muscle strength measurements. RESULTS: Manual muscle strength testing showed that most muscles recover to grade 3 or 4. Average grip strength recovery, as percentage of the uninjured hand, was 83%. Pinch strength recovery was 75%, 58% and 39% in patients with ulnar, median and combined nerve injuries, respectively. The RIHM measurements revealed a poor recovery of the ulnar nerve innervated muscles in particular (26-37%). No significant correlation (Pearson) was found between the measurements of the RIHM and grip strength. Pinch strength was significantly correlated with strength of the abduction of thumb and opposition of the thumb strength (r 0.55 and 0.72, p = 0.026, 0.002) as measured with the RIHM. CONCLUSION: While manual muscle strength testing and grip strength measurements show a reasonable to good recovery, measurements of the intrinsic muscles by means of the RIHM showed poor recovery of intrinsic muscle strength after peripheral nerve injury. No correlation was found between the recovery of intrinsic muscle strength and grip strength measurements.

Adolescent↗

PubMed1997

Smooth muscle myosin light chain kinase is transiently expressed in skeletal muscle during embryogenesis and muscle regeneration both in vivo and in vitro.

By using a polyclonal antibody raised against smooth muscle Myosin Light Chain Kinase of adult chicken we show that the 135 kDa smooth muscle Myosin Light Chain Kinase isoform is present in neonatal and regenerating rat skeletal muscle, as well as in adult atrial myocardium. No reaction was evident in adult skeletal muscle fibres. In neonatal and in early regenerating muscle smooth muscle Myosin Light Chain Kinase is associated with embryonic myosin as revealed by their co-presence in muscle fibres. Experiments in vitro show the same results in myotubes. In atrial myocardium there is a patchy positivity in certain group of myocytes. Immunoblotting experiments show in muscle cell cultures, in neonatal and in regenerating skeletal muscle a protein band with electrophoretic mobility corresponding to that of smooth muscle Myosin Light Chain Kinase. These results suggest that the expression of smooth muscle Myosin Light Chain Kinase is not fully tissue-specific and that regulation of the contractile machinery could be different during myogenesis and in adulthood, in relation to the peculiar dynamic characteristics of developing muscles.

Animals↗

PubMed1993

Muscle damage is not a function of muscle force but active muscle strain.

Contractile properties of rabbit tibialis anterior muscles were measured after eccentric contraction to investigate the mechanism of muscle injury. In the first experiment, two groups of muscles were strained 25% of the muscle fiber length at identical rates. However, because the timing of the imposed length change relative to muscle activation was different, the groups experienced dramatically different muscle forces. Because muscle maximum tetanic tension and other contractile parameters measured after 30 min of cyclic activity with either strain timing pattern were identical (P > 0.4), we concluded that muscle damage was equivalent despite very different imposed forces. This result was supported by a second experiment in which the same protocol was performed at one-half the strain (12.5% muscle fiber length). Again, there was no difference in maximum tetanic tension after cyclic 12.5% strain with either strain timing. Data from both experiments were analyzed by two-way analysis of variance, which revealed a highly significant effect of strain magnitude (P < 0.001) but no significant effect of stretch timing (P > 0.7). We interpret these data to signify that it is not high force per se that causes muscle damage after eccentric contraction but the magnitude of the active strain (i.e., strain during active lengthening). This conclusion was supported by morphometric analysis showing equivalent area fractions of damaged muscle fibers that were observed throughout the muscle cross section. The active strain hypothesis is described in terms of the interaction between the myofibrillar cytoskeleton, the sarcomere, and the sarcolemma.

Animals↗

PubMed2000

[A case of sarcoid myopathy presenting muscle pain and muscle weakness and with muscle MRI abnormality].

We experienced a 70-year-old female diagnosed as sarcoidosis. She complained bilateral femoral pain from 70-year-old. 3 months after the onset, she developed muscle weakness extending to her upper extremities with high fever of 38-39 degrees C. The erythema appeared at the right femoral region 4 months after the onset. She admitted to our hospital because of further evaluation. When she was admitted, she had tenderness on grasping the femoral muscles, proximal limb muscle weakness and Gowers' sign. On laboratory examination, CRP, aldorase, myoglobin, lysozyme were increased mildly. The EMG demonstrated a myogenic pattern. Muscle biopsy performed from the left quadriceps femoris muscle revealed non-caseating granuloma and muscle fiber necrosis. A diagnosis of muscle sarcoidosis was made from the biopsy findings and the clinical features. With oral prednisolone administration, muscle weakness and other clinical features improved gradually. On muscle MRI, multiple small high intensity areas were scattered in the femoral muscles. Muscle MRI is considered to be useful for differential diagnosis of muscle sarcoidosis.

Aged↗

PubMed2000

Muscle actin genes and muscle cells in the appendicularian, Oikopleura longicauda: phylogenetic relationships among muscle tissues in the urochordates.

Appendicularians (larvaceans) are planktonic tunicates. They possess a tail throughout their life, which marks a distinct difference between appendicularians and the other tunicate groups, including salps, doliolids, pyrosomes, and ascidians. We isolated cDNA clones encoding muscle-type and cytoplasmic-type actin isoforms from the appendicularian, Oikopleura longicauda. The types of the actin isoforms were confirmed by amino acid identities in the diagnostic residues compared to those of the other chordate muscle and cytoplasmic actins. Interestingly the appendicularian muscle actin isoform sequence has an intermediate feature between the ascidian tail (larval) muscle actin isoform and the body-wall (adult) muscle actin isoform. Analysis of a genomic clone from a muscle actin gene revealed that it contains only one intron in the coding region. It is located at a position that does not correspond to those of any introns reported in other deuterostome actin genes. Whole-mount in situ hybridization shows that the muscle actin transcript is detected specifically in the tail muscle cells of late tailbud-stage embryos. A signal is also found transiently in the region where the heart will form. In adults, the gene is expressed in tail muscle cells but not in the heart. Together with results of cytochemical and histochemical studies demonstrating the structure of muscle tissue, the present study highlights characteristics of appendicularian muscle organization, which are compared with those of the larval and adult muscle of ascidians.

Actins↗

PubMed2001

Muscle activity and muscle agrin regulate the organization of cytoskeletal proteins and attached acetylcholine receptor (AchR) aggregates in skeletal muscle fibers.

In innervated skeletal muscle fibers, dystrophin and beta-dystroglycan form rib-like structures (costameres) that appear as predominantly transverse stripes over Z and M lines. Here, we show that the orientation of these stripes becomes longitudinal in denervated muscles and transverse again in denervated electrically stimulated muscles. Skeletal muscle fibers express nonneural (muscle) agrin whose function is not well understood. In this work, a single application of > or = 10 nM purified recombinant muscle agrin into denervated muscles preserved the transverse orientation of costameric proteins that is typical for innervated muscles, as did a single application of > or = 1 microM neural agrin. At lower concentration, neural agrin induced acetylcholine receptor aggregates, which colocalized with longitudinally oriented beta-dystroglycan, dystrophin, utrophin, syntrophin, rapsyn, and beta 2-laminin in denervated unstimulated fibers and with the same but transversely oriented proteins in innervated or denervated stimulated fibers. The results indicate that costameres are plastic structures whose organization depends on electrical muscle activity and/or muscle agrin.

Agrin↗

PubMed1984

Chordate muscle actins differ distinctly from invertebrate muscle actins. The evolution of the different vertebrate muscle actins.

A total of 30 actins from various chordate and invertebrate muscle sources were either characterized by full amino acid sequence data or typed by those partial sequences in the NH2-terminal tryptic peptide which are known to be specific markers for different actin isoforms. The results show that most, if not all, invertebrate muscle actins are homologous to each other and to the isoforms recognized as vertebrate cytoplasmic actins. In contrast the actin forms typically found in muscle cells of warm-blooded vertebrates are noticeably different from invertebrate muscle actins and seem to have appeared in evolution already with the origin of chordates. During subsequent vertebrate evolution there has been a high degree of sequence conservation similar or stronger than that seen in histone H4. Urochordates, Cephalochordates and probably also Agnathes express only one type of muscle actin. Two types, a striated muscle-specific form and a smooth muscle form, are already observed in Chondrichthyes and Osteichthyes. Later in evolution, with the origin of reptiles, both muscle actins seem to have duplicated again; the striated muscle type branched into a skeletal- and cardiac-specific form, while the smooth muscle form duplicated into a vascular- and stomach-specific type. These findings support the hypothesis that each of the four muscle actins of warm-blooded vertebrates are coded for by a small number and possibly only one functional gene.

Actins↗

PubMed2000

Ca2+- and Sr2+-activation properties of muscle fibres from a muscle receptor organ and the associated extrafusal muscle of the crab and crayfish.

In this study on decapod crustaceans, we examined the Ca2+- and Sr2+-activation properties of skeletal muscle fibres from an identified proprioceptor, the thoracic coxal muscle receptor organ (TCMRO) and its extrafusal promotor muscle fibres. Proprioceptors and extrafusal muscles were isolated from a walking leg from the crayfish (Cherax destructor) and the rear swimming leg of the mud crab (Scylla serrata). The crayfish and mud crab TCMROs had very low Hill coefficient (nCa) values (1.86 +/- 0.08 and 1.64 +/- 0.03, respectively). In comparison to other skeletal muscle fibre types these low Hill coefficients would enable the length of the receptor muscles to be finely controlled over a wide range of [Ca2+]. Maximum force was found to be significantly lower in the TCMROs (crayfish: 5.76 +/- 0.98; crab: 4.80 +/- 0.56 Ncm(-2)), compared to their associated extrafusal promotor muscle fibres (crayfish: 10.69 +/- 1.63; crab: 20.07 +/- 1.98 Ncm(-2)), which is consistent with their sensory role. The muscle fibres of the crayfish TCMRO had faster contractile properties than the mud crab TCMRO, we discuss how these contractile properties relate to the type of locomotion undergone by each leg. The mud crab 'red' promotor and all crayfish promotor fibres were characterised as slow with low Hill coefficients (nCa: crayfish: 3.22 +/- 0.29; crab: 3.34 +/- 0.29) and a contractile apparatus with a high sensitivity to Ca2+ (pCa50: crayfish: 6.42 +/- 0.03; crab: 6.18 +/- 0.03). In contrast the 'white' mud crab promotor fibres from the swimming leg had contractile properties that were characteristic of fast fibres with a high mean Hill coefficient (nCa: 5.27 +/- 0.76) and a lower Ca2+ sensitivity (pCa50: 6.03 +/- 0.03). The sensitivity of the contractile apparatus to Sr2+ was very low (range of mean pSr50: 4.23 +/- 0.03-3.48 +/- 0.06) and low force levels were produced in comparison to that produced with Ca2+. The results of this study show that the muscle fibres of the sensory receptor, produce less force and have been adapted to enable the length of the receptor to be finely set in relation to the length of the extrafusal muscle. We discuss how the striated fibres of the receptor have been adapted to perform a sensory role and how this is related to the type of locomotion undergone by the legs. We also discuss how the fibre types of the extrafusal muscle have adapted to the mode of locomotion.

Animals↗

PubMed2003

Overexpression of HSP70 in mouse skeletal muscle protects against muscle damage and age-related muscle dysfunction.

Ageing is associated with skeletal muscle atrophy, a deficit in force generation, an increased susceptibility to contraction-induced injury, and a permanent force deficit following severe injury. Muscles of young mice adapt rapidly following exercise by an increase in the production of heat shock proteins (HSPs), whereas muscles of old mice show a severely diminished response. We hypothesized that overexpression of HSP70 in muscle throughout life would reduce age-related changes in function. The maximum tetanic force of extensor digitorum longus (EDL) muscles of adult and old wild-type (WT) and HSP70 overexpressor transgenic mice was determined. EDL muscles were subjected to damaging lengthening contractions and the ability to generate force was assessed for up to 28 days following the contractions. Overexpression of HSP70 in muscles of old transgenic mice prevented the specific force deficit observed in muscles of old WT mice. The complete recovery of muscles of old HSP70 transgenic mice by 14 days following the contraction protocol was in contrast to the 44% force deficit, which remained in muscles of old WT mice at 28 days following the protocol. These data indicate that a diminished production of HSP70 in muscles of old mammals has a major effect on age-related functional deficits.

Aging↗

PubMed2001

Selective cricothyroid muscle reinnervation by muscle-nerve-muscle neurotization.

OBJECTIVE: To determine if selective reinnervation of the cricothyroid muscle could be achieved with muscle-nerve-muscle neurotization. DESIGN: Case series. SETTING: Tertiary referral center. PATIENTS: Three consecutive patients with high vagal lesions that resulted in unilateral laryngeal paralysis. INTERVENTIONS: Patients underwent laryngeal reinnervation with ansa hypoglossi to recurrent laryngeal nerve anastomosis. In addition, patients underwent selective cricothyroid muscle reinnervation by muscle-nerve-muscle neurotization technique. MAIN OUTCOME MEASURES: Objective and subjective improvement in voice quality and electromyographic evidence of selective reinnervation of the cricothyroid muscle. RESULTS: All patients recovered normal or near-normal speaking voice and had normal objective measures of voice quality. They also showed electromyographic evidence of cricothyroid muscle reinnervation. CONCLUSION: The muscle-nerve-muscle neurotization technique was successful in providing selective reinnervation of the cricothyroid muscle in our 3 patients.

Adult↗

PubMed1993

Muscle length-force characteristics in relation to muscle architecture: a bilateral study of gastrocnemius medialis muscles of unilaterally immobilized rats.

The geometry of rat gastrocnemius medialis muscle (GM) was studied at different muscle lengths. In addition, the number of sarcomeres in series within fibres was estimated. For muscles of immobilized legs (i.e. GM was held at in vivo smallest length) as well as those of the contralateral legs, comparison was made with controls of similar age. Immobilization periods of 4 and 6 weeks were used. For immobilized GM muscles, the number of sarcomeres in series was lower only within distal fibres after 4 weeks of immobilization. Aponeuroses were 25% shorter after both immobilization periods and no differences were found for fibre and aponeurosis angle. For GM of contralateral legs no difference with respect to controls was found regarding the number of sarcomeres in series. Aponeuroses were approximately 15% shorter and the fibre and the aponeurosis angle were also smaller. Based on these geometrical differences, it was expected that both experimental muscles should exert force over a smaller range of muscle length than controls. However, for immobilized muscles a similar range of length was found for which a possible explanation could be the more compliant aponeurosis. For contralateral muscle a 2-mm larger length range as well as a change of distribution of optimal fibre length with respect to optimal muscle length was found. For immobilized muscles indications of a distribution of optimal fibre lengths were also found but these did not differ from those of the controls. The results for contralateral muscles would indicate that the distribution may be changed under the influence of an altered use of the limb and that this may be an important factor determining the length range of active force generation.

Animals↗

PubMed1997

Phasic and tonic stretch reflexes in muscles with few muscle spindles: human jaw-opener muscles.

We investigated phasic and tonic stretch reflexes in human jaw-opener muscles, which have few, if any, muscle spindles. Jaw-unloading reflexes were recorded for both opener and closer muscles. Surface electromyographic (EMG) activity was obtained from left and right digastric and superficial masseter muscles, and jaw orientation and torques were recorded. Unloading of jaw-opener muscles elicited a short-latency decrease in EMG activity (averaging 20 ms) followed by a short-duration silent period in these muscles and sometimes a short burst of activity in their antagonists. Similar behavior in response to unloading was observed for spindle-rich jaw-closer muscles, although the latency of the silent period was statistically shorter than that observed for jaw-opener muscles (averaging 13 ms). Control studies suggest that the jaw-opener reflex was not due to inputs from either cutaneous or periodontal mechanoreceptors. In the unloading response of the jaw openers, the tonic level of EMG activity observed after transition to the new jaw orientation was monotonically related to the residual torque and orientation. This is consistent with the idea that the tonic stretch reflex might mediate the change in muscle activation. In addition, the values of the static net joint torque and jaw orientation after the dynamic phase of unloading were related by a monotonic function resembling the invariant characteristic recorded in human limb joints. The torque-angle characteristics associated with different initial jaw orientations were similar in shape but spatially shifted, consistent with the idea that voluntary changes in jaw orientation might be associated with a change in a single parameter, which might be identified as the threshold of the tonic stretch reflex. It is suggested that functionally significant phasic and tonic stretch reflexes might not be mediated exclusively by muscle spindle afferents. Thus, the hypothesis that central modifications in the threshold of the tonic stretch reflex underlie the control of movement may be applied to the jaw system.

Electromyography↗

PubMed2003

Transgenic and tissue culture analyses of the muscle creatine kinase enhancer Trex control element in skeletal and cardiac muscle indicate differences in gene expression between muscle types.

The muscle creatine kinase (MCK) gene is expressed at high levels only in differentiated skeletal and cardiac muscle. The activity of the cloned enhancer-promoter has previously been shown to be dependent on the Trex element which is specifically bound by a yet unidentified nuclear factor, TrexBF. We have further characterized the function of the Trex site by comparing wild-type and Trex-mutated MCK transgenes in five mouse skeletal muscles: quadriceps, extensor digitorum longus (EDL), soleus, diaphragm, and distal tongue, as well as in heart ventricular muscle. Several types of statistical analysis including analysis of variance (ANOVA) and rank sum tests were used to compare expression between muscle types and between constructs. Upon mutation of the Trex site, median transgene expression levels decreased 3- to 120-fold in the muscles examined, with statistically significant differences in all muscles except the EDL. Expression in the largely slow soleus muscle was more affected than in the EDL, and expression in the distal tongue and diaphragm muscles was affected more than in soleus. Median expression of the transgene in ventricle decreased about 18-fold upon Trex mutation. Transfections into neonatal rat myocardiocytes confirmed the importance of the Trex site for MCK enhancer activity in heart muscle, but the effect is larger in transgenic mice than in cultured cells.

Animals↗