Krüppel-like factor 10 regulates the contractile properties of skeletal muscle fibers in mice.

INTRODUCTION/AIMS: Klf10 is a member of the Krüppel-like family of transcription factors, which is implicated in mediating muscle structure (fiber size, organization of the sarcomere), muscle metabolic activity (respiratory chain), and passive force. The aim of this study was to further characterize the roles of Klf10 in the contractile properties of skeletal muscle fibers. METHODS: Fifty-two single fibers were extracted from female wild-type (WT) and Klf10 knockout (KO) oxidative (soleus) and glycolytic (extensor digitorum longus [EDL]) skinned muscles. Each fiber was immersed successively in relaxing (R), washing (W), and activating (A) solutions. Calcium was included in the activating solution to induce a maximum contraction of the fiber. The maximum force (Fmax ) was measured and normalized to the cross-sectional area to obtain the maximum stress (Stressmax ). After a steady state in contraction was reached, a quick stretch-release was performed; the force at the maximum stretch (Fstretch ) was measured and the stiffness was assessed. RESULTS: Deletion of the Klf10 gene induced changes in the contractile parameters (Fmax , Stressmax , Stiffness), which were lower and higher for soleus and EDL fibers compared with littermates, respectively. These measurements also revealed changes in the proportion and resistance of attached cross-bridges. DISCUSSION: Klf10 plays a major role in the homeostasis of the contractile behavior of skeletal muscle fibers in a muscle fiber type-specific manner. These findings further implicate important roles for Klf10 in skeletal muscle function and shed new light on understanding the molecular processes regulating the contractility of skeletal muscle fibers.

Impact of TIEG1 on the structural properties of fast- and slow-twitch skeletal muscle.

INTRODUCTION: Transforming growth factor-beta (TGF-ß)-inducible early gene-1 (TIEG1) is a transcription factor that is highly expressed in skeletal muscle. The purpose of this study was to characterize the structural properties of both fast-twitch (EDL) and slow-twitch (soleus) muscles in the hindlimb of TIEG1-deficient (TIEG1-/- ) mice. METHODS: Ten slow and 10 fast muscles were analyzed from TIEG1-/- and wild-type (WT) mice using MRI texture (MRI-TA) and histological analyses. RESULTS: MRI-TA could discriminate between WT slow and fast muscles. Deletion of the TIEG1 gene led to changes in the texture profile within both muscle types. Specifically, muscle isolated from TIEG1-/- mice displayed hypertrophy, hyperplasia, and a modification of fiber area distribution. CONCLUSIONS: We demonstrated that TIEG1 plays an important role in the structural properties of skeletal muscle. This study further implicates important roles for TIEG1 in the development of skeletal muscle and suggests that defects in TIEG1 expression and/or function may be associated with muscle disease. Muscle Nerve 55: 410-416, 2017.

Viscoelastic shear properties of in vivo thigh muscles measured by MR elastography.

PURPOSE: To measure the viscoelastic properties of passive thigh muscles using multifrequency magnetic resonance elastography (MMRE) and rheological models. MATERIALS AND METHODS: Four muscles in five volunteers underwent MMRE tests set up inside a 1.5T magnetic resonance imaging (MRI) scanner. Compression excitation was generated with a driver attached around the thigh, and waves were generated at 70, 90, and 110 Hz. In vivo experimental viscoelastic parameters (G(ω) = G' + i G″) were extracted from the wavelength and attenuation measurements along a local profile in the direction of the wave's displacement. The data-processing method was validated on a phantom using MMRE and RheoSpectris tests. The complex modulus (G(ω)) related to elasticity (µ) and viscosity (η) was then determined using four rheological models. RESULTS: Zener was the best-fit model (χ ∼0.35 kPa) for the rheological parameters of all muscles. Similar behaviors for the elastic components for each muscle were found for the Zener and springpot models. The gracilis muscle showed higher elastic values (about 2 kPa) in both models compared to other muscles. The α-values for each muscle was equivalent to the ratio G″/G' at 90 Hz. CONCLUSION: MMRE tests associated with data processing demonstrated that the complex shear modulus G(ω) of passive muscles could be analyzed using two rheological models. The viscoelastic data can be used as a reference for future assessment of muscular dysfunction. J. Magn. Reson. Imaging 2015. J. Magn. Reson. Imaging 2016;43:1423-1433.

Development of an inverse approach for the characterization of in vivo mechanical properties of the lower limb muscles.

The purpose of this study was to develop an inverse method, coupling imaging techniques with numerical methods, to identify the muscle mechanical behavior. A finite element model updating (FEMU) was developed in three main interdependent steps. First, a 2D FE modeling, parameterized by a Neo-Hookean behavior (C10 and D), was developed from a segmented thigh muscle 1.5T MRI (magnetic resonance imaging). Thus, a displacement field was simulated for different static loadings (contention, compression, and indentation). Subsequently, the optimal mechanical test was determined from a sensitivity analysis. Second, ultrasound parameters (gain, dynamic, and frequency) were optimized on the thigh muscles in order to apply the digital image correlation (DIC), allowing the measurement of an experimental displacement field. Third, an inverse method was developed to identify the Neo-Hookean parameters (C10 and D) by performing a minimization of the distance between the simulated and measured displacement fields. To replace the experimental data and to quantify the identification error, a numerical example was developed. The result of the sensitivity analysis showed that the compression test was more adapted to identify the Neo-Hookean parameters. Ultrasound images were recorded with a frequency, gain, and dynamic of 9 MHz, 34 dB, 42 dB, respectively. In addition, the experimental noise on displacement field measurement was estimated to be 0.2 mm. The identification performed on the numerical example revealed a low error for the C10 (<3%) and D (<7%) parameters with the experimental noise. This methodology could have an impact in the scientific and medical fields. A better knowledge of the muscle behavior will help to follow treatment and to ensure accurate medical procedures during the use of robotic devices.

Applications of ultrasound elastography to hand and upper limb disorders.

Ultrasound elastography is a recently developed method for accurate measurement of soft tissue stiffness in addition to the clinician's subjective evaluation. The present review briefly describes the ultrasound elastography techniques and outlines clinical applications for tendon, muscle, nerve, skin and other soft tissues of the hand and upper limb. Strain elastography provides a qualitative evaluation of the stiffness, and shear-wave elastography generates quantitative elastograms superimposed on a B-mode image. The stiffness in degenerative tendinopathy and/or tendon injury was significantly lower than in a normal tendon in several studies. Elastography is also a reliable method to evaluate functional muscle activity, compared to conventional surface electromyography. The median nerve is consistently stiffer in patients with carpal tunnel syndrome than in healthy subjects, on whatever ultrasound elastography technique. Elastography distinguishes normal skin from scars and can be used to evaluate scar severity and treatment. Elastography has huge clinical applications in musculoskeletal tissues. Continued development of systems and increased training of clinicians will expand our knowledge of elastography and its clinical applications in the future.

Analysis of liver viscosity behavior as a function of multifrequency magnetic resonance elastography (MMRE) postprocessing.

PURPOSE: To analyze the relevance of the viscosity measurement as a liver diagnostic marker. MATERIALS AND METHODS: To determine the level of fibrosis, a Fibroscan test was performed on 40 subjects (10 healthy volunteers and 30 patients). Subsequently, multifrequency magnetic resonance elastography (MMRE) tests were made with a pneumatic driver at 60, 70, and 80 Hz. Phase images were analyzed with two different postprocessing methods, without (Method 1) and with (Method 2) the inversion algorithm (IA), using rheological models (Voigt, springpot) in order to characterize the viscoelastic properties (viscosity: η and elasticity: µ). RESULTS: MRE cartography of the viscous tendency (G″MRE_M2 ) measured within the region of interest (ROI) of the liver increased as a function of the level of fibrosis. Similar results were also obtained for the viscosity (ηmodels_M1 ) calculated with a postprocessing without IA. However, the viscosity (ηmodels_M2 ) remained constant with the stage of fibrosis when the postprocessing was composed of an IA. The experimental (µMRE_M1 and G'MRE_M2 ) and rheological (µmodels_M2 and µmodels_M1 ) elasticities always increased with the level of fibrosis regardless of the postprocessing method. CONCLUSION: The variation of the liver viscosity parameter as a function of postprocessing revealed that this parameter should be further investigated to demonstrate its relevance in clinical practice.

A possible clinical tool to depict muscle elasticity mapping using magnetic resonance elastography.

INTRODUCTION: Characterization of muscle elasticity will improve the diagnosis and treatment of muscle disorders. The purpose is to compare the use of magnetic resonance elastography (MRE) and ultrasound elastography (USE) techniques to elucidate the MRE cartography of thigh muscles. METHODS: Both elastography techniques were performed on 5 children and 7 adults. Quantitative (MRE) and qualitative (USE) cartographies of muscle elasticity, as a function of muscle state and age, were obtained with shear waves and manual compression of the ultrasound probe, respectively. RESULTS: Similar cartographies of muscle elasticity were obtained with the 2 methods. The combination of both imaging techniques results in an improved depiction of the physiological changes associated with muscle state and age. CONCLUSIONS: This study demonstrates the feasibility of MRE for use as a clinical tool in the characterization of neuromuscular pathologies and for assessing the efficacy of specific treatments for muscle related diseases.

Cutoff values for alcoholic liver fibrosis using magnetic resonance elastography technique.

BACKGROUND: Due to the lack of cutoff values validated for specific liver diseases, the purpose of this study was to set up specific magnetic resonance elastography (MRE) cutoff values for asymptomatic liver fibrosis in alcoholic patients. METHODS: Ninety patients underwent 3 clinical exams. The liver stiffness was measured locally with the Fibroscan, and globally through cartographies of shear modulus generated with MRE. The Fibroscan method was chosen as the gold standard to classify the fibrosis. The liver score was also obtained with the Fibrometer A, and the diagnostic performance of the methods was analyzed with receiver-operating characteristic (ROC) curves and cutoff values were calculated. RESULTS: Spearman correlation and area under the ROC curve revealed that MRE is a better diagnostic method than the Fibrometer A, to identify various levels of fibrosis. The results showed that the Fibrometer A was adapted for severe fibrosis. The MRE cutoff values are F1:2.20 kPa, F2:2.57 kPa, F3:3.31 kPa, and F4:4 kPa and were not influenced by the glutamic oxaloacetic transaminase level. By using the ultrasound cutoff values attributed for alcoholism, 66% of patients had a similar liver fibrosis diagnosis as the MRE cutoffs. However, both imaging techniques did not provide the same distribution for minor fibrosis. CONCLUSIONS: None of the imaging techniques (Fibroscan, MRE) could replace the gold standard of the biopsy. However, due to the risk and the unnecessary procedure for the present recruited alcoholic patients, the Fibroscan method was chosen as the reference. Since MRE is currently being used as a clinical exam, the present MRE cutoffs could aid clinicians with their diagnosis of liver fibrosis for alcoholism disease.

Assessing reliability and validity of different stiffness measurement tools on a multi-layered phantom tissue model.

Changes in the mechanical properties (i.e., stiffness) of soft tissues have been linked to musculoskeletal disorders, pain conditions, and cancer biology, leading to a rising demand for diagnostic methods. Despite the general availability of different stiffness measurement tools, it is unclear as to which are best suited for different tissue types and the related measurement depths. The study aimed to compare different stiffness measurement tools' (SMT) reliability on a multi-layered phantom tissue model (MPTM). A polyurethane MPTM simulated the four layers of the thoracolumbar region: cutis (CUT), subcutaneous connective tissue (SCT), fascia profunda (FPR), and erector spinae (ERS), with varying stiffness parameters. Evaluated stiffness measurement tools included Shore Durometer, Semi-Electronic Tissue Compliance Meter (STCM), IndentoPRO, MyotonPRO, and ultrasound imaging. Measurements were made by two independent, blinded examiners. Shore Durometer, STCM, IndentoPRO, and MyotonPRO reliably detected stiffness changes in three of the four MPTM layers, but not in the thin (1 mm thick) layer simulating FPR. With ultrasound imaging, only stiffness changes in layers thicker than 3 mm could be measured reliably. Significant correlations ranging from 0.70 to 0.98 (all p < 0.01) were found. The interrater reliability ranged from good to excellent (ICC(2,2) = 0.75-0.98). The results are encouraging for researchers and clinical practitioners as the investigated stiffness measurement tools are easy-to-use and comparatively affordable.

TIEG1-null tenocytes display age-dependent differences in their gene expression, adhesion, spreading and proliferation properties.

The remodeling of extracellular matrix is a crucial mechanism in tendon development and the proliferation of fibroblasts is a key factor in this process. The purpose of this study was to further elucidate the role of TIEG1 in mediating important tenocyte properties throughout the aging process. Wildtype and TIEG1 knockout tenocytes adhesion, spreading and proliferation were characterized on different substrates (fibronectin, collagen type I, gelatin and laminin) and the expression levels of various genes known to be involved with tendon development were analyzed by RT-PCR. The experiments revealed age-dependent and substrate-dependent properties for both wildtype and TIEG1 knockout tenocytes. Taken together, our results indicate an important role for TIEG1 in regulating tenocytes adhesion, spreading, and proliferation throughout the aging process. Understanding the basic mechanisms of TIEG1 in tenocytes may provide valuable information for treating multiple tendon disorders.

Serum and Soleus Metabolomics Signature of Klf10 Knockout Mice to Identify Potential Biomarkers.

The transcription factor Krüppel-like factor 10 (Klf10), also known as Tieg1 for TGFß (Inducible Early Gene-1) is known to control numerous genes in many cell types that are involved in various key biological processes (differentiation, proliferation, apoptosis, inflammation), including cell metabolism and human disease. In skeletal muscle, particularly in the soleus, deletion of the Klf10 gene (Klf10 KO) resulted in ultrastructure fiber disorganization and mitochondrial metabolism deficiencies, characterized by muscular hypertrophy. To determine the metabolic profile related to loss of Klf10 expression, we analyzed blood and soleus tissue using UHPLC-Mass Spectrometry. Metabolomics analyses on both serum and soleus revealed profound differences between wild-type (WT) and KO animals. Klf10 deficient mice exhibited alterations in metabolites associated with energetic metabolism. Additionally, chemical classes of aromatic and amino-acid compounds were disrupted, together with Krebs cycle intermediates, lipids and phospholipids. From variable importance in projection (VIP) analyses, the Warburg effect, citric acid cycle, gluconeogenesis and transfer of acetyl groups into mitochondria appeared to be possible pathways involved in the metabolic alterations observed in Klf10 KO mice. These studies have revealed essential roles for Klf10 in regulating multiple metabolic pathways whose alterations may underlie the observed skeletal muscle defects as well as other diseases.

Deciphering the Role of Klf10 in the Cerebellum.

Recent studies have demonstrated a new role for Klf10, a Krüppel-like transcription factor, in skeletal muscle, specifically relating to mitochondrial function. Thus, it was of interest to analyze additional tissues that are highly reliant on optimal mitochondrial function such as the cerebellum and to decipher the role of Klf10 in the functional and structural properties of this brain region. In vivo (magnetic resonance imaging and localized spectroscopy, behavior analysis) and in vitro (histology, spectroscopy analysis, enzymatic activity) techniques were applied to comprehensively assess the cerebellum of wild type (WT) and Klf10 knockout (KO) mice. Histology analysis and assessment of locomotion revealed no significant difference in Klf10 KO mice. Diffusion and texture results obtained using MRI revealed structural changes in KO mice characterized as defects in the organization of axons. These modifications may be explained by differences in the levels of specific metabolites (myo-inositol, lactate) within the KO cerebellum. Loss of Klf10 expression also led to changes in mitochondrial activity as reflected by a significant increase in the activity of citrate synthase, complexes I and IV. In summary, this study has provided evidence that Klf10 plays an important role in energy production and mitochondrial function in the cerebellum.

Improved Ultrasound Attenuation Measurement Method for the Non-invasive Evaluation of Hepatic Steatosis Using FibroScan.

Controlled attenuation parameter (CAP) is a measurement of ultrasound attenuation used to assess liver steatosis non-invasively. However, the standard method has some limitations. This study assessed the performance of a new CAP method by ex vivo and in vivo assessments. The major difference with the new method is that it uses ultrasound data continuously acquired during the imaging phase of the FibroScan examination. Seven reference tissue-mimicking phantoms were used to test the performance. In vivo performance was assessed in two cohorts (in total 195 patients) of patients using magnetic resonance imaging proton density fat fraction (MRI-PDFF) as a reference. The precision of CAP was improved by more than 50% on tissue-mimicking phantoms and 22%-41% in the in vivo cohort studies. The agreement between both methods was excellent, and the correlation between CAP and MRI-PDFF improved in both studies (0.71 to 0.74; 0.70 to 0.76). Using MRI-PDFF as a reference, the diagnostic performance of the new method was at least equal or superior (area under the receiver operating curve 0.889-0.900, 0.835-0.873). This study suggests that the new continuous CAP method can significantly improve the precision of CAP measurements ex vivo and in vivo.

Ultrasound image processing to estimate the structural and functional properties of mouse skeletal muscle.

Noninvasive imaging techniques are increasingly used for monitoring muscle behavior in mice. However, muscle is a complex tissue that exhibits different properties under passive and active conditions. In addition to structural properties, it is also important to analyze functional characteristics. At present, such information can be obtained with ultrasound elastography. However, this technique is poorly used for small rodent models (mice and gerbils). Thus, this study aims at establish referent hindlimb muscle data, and experimental guidelines, for wild-type (WT) control mice as well as the TIEG1 knockout (KO) mouse model that is known to exhibit skeletal muscle defects. Ultrasound was performed with the Aixplorer machine using a SLH 20-6 linear transducer probe (2.8 cm footprint). A region of interest (ROI) was placed around a superficial group of muscles. Subsequently, from the B-mode image, a classification of all the muscles and ultrasound biomarkers such as echo intensity and texture anisotropy have been determined. The influence of the gain setting (from 40% to 70%) was analyzed on these parameters. Moreover, the elasticity (E) was also measured within the ROI. This study provides a suitable methodology for collecting experimental data: 1) the correct range of gain (between 50% and 70%) to apply for the ultrasound measurement of muscle structure, 2) the structural and functional referent data for a group of healthy muscles, 3) the gray scale index, the texture anisotropy and the elasticity (ETIEG1 KO = 36.1 ± 10.3 kPa, EWT = 44.4 ± 13.4 kPa) parameters, which were obtained for a group of muscles as a function of genotype.

Novel role of Tieg1 in muscle metabolism and mitochondrial oxidative capacities.

AIM: Tieg1 is involved in multiple signalling pathways, human diseases, and is highly expressed in muscle where its functions are poorly understood. METHODS: We have utilized Tieg1 knockout (KO) mice to identify novel and important roles for this transcription factor in regulating muscle ultrastructure, metabolism and mitochondrial functions in the soleus and extensor digitorum longus (EDL) muscles. RNA sequencing, immunoblotting, transmission electron microscopy, MRI, NMR, histochemical and mitochondrial function assays were performed. RESULTS: Loss of Tieg1 expression resulted in altered sarcomere organization and a significant decrease in mitochondrial number. Histochemical analyses demonstrated an absence of succinate dehydrogenase staining and a decrease in cytochrome c oxidase (COX) enzyme activity in KO soleus with similar, but diminished, effects in the EDL. Decreased complex I, COX and citrate synthase (CS) activities were detected in the soleus muscle of KO mice indicating altered mitochondrial function. Complex I activity was also diminished in KO EDL. Significant decreases in CS and respiratory chain complex activities were identified in KO soleus. 1 H-NMR spectra revealed no significant metabolic difference between wild-type and KO muscles. However, 31 P spectra revealed a significant decrease in phosphocreatine and ATPγ. Altered expression of 279 genes, many of which play roles in mitochondrial and muscle function, were identified in KO soleus muscle. Ultimately, all of these changes resulted in an exercise intolerance phenotype in Tieg1 KO mice. CONCLUSION: Our findings have implicated novel roles for Tieg1 in muscle including regulation of gene expression, metabolic activity and organization of tissue ultrastructure. This muscle phenotype resembles diseases associated with exercise intolerance and myopathies of unknown consequence.

TIEG1-NULL OSTEOCYTES DISPLAY DEFECTS IN THEIR MORPHOLOGY, DENSITY AND SURROUNDING BONE MATRIX.

Through the development of TGFß-inducible early gene-1 (TIEG1) knockout (KO) mice, we have demonstrated that TIEG1 plays an important role in osteoblast-mediated bone mineralization, and in bone resistance to mechanical strain. To further investigate the influence of TIEG1 in skeletal maintenance, osteocytes were analyzed by transmission electron microscopy using TIEG1 KO and wild-type mouse femurs at one, three and eight months of age. The results revealed an age-dependent change in osteocyte surface and density, suggesting a role for TIEG1 in osteocyte development. Moreover, there was a decrease in the amount of hypomineralized bone matrix surrounding the osteocytes in TIEG1 KO mice relative to wild-type controls. While little is known about the function or importance of this hypomineralized bone matrix immediately adjacent to osteocytes, this study reveals significant differences in this bone microenvironment and suggests that osteocyte function may be compromised in the absence of TIEG1 expression.

Development of a novel multiphysical approach for the characterization of mechanical properties of musculotendinous tissues.

At present, there is a lack of well-validated protocols that allow for the analysis of the mechanical properties of muscle and tendon tissues. Further, there are no reports regarding characterization of mouse skeletal muscle and tendon mechanical properties in vivo using elastography thereby limiting the ability to monitor changes in these tissues during disease progression or response to therapy. Therefore, we sought to develop novel protocols for the characterization of mechanical properties in musculotendinous tissues using atomic force microscopy (AFM) and ultrasound elastography. Given that TIEG1 knockout (KO) mice exhibit well characterized defects in the mechanical properties of skeletal muscle and tendon tissue, we have chosen to use this model system in the present study. Using TIEG1 knockout and wild-type mice, we have devised an AFM protocol that does not rely on the use of glue or chemical agents for muscle and tendon fiber immobilization during acquisition of transversal cartographies of elasticity and topography. Additionally, since AFM cannot be employed on live animals, we have also developed an ultrasound elastography protocol using a new linear transducer, SLH20-6 (resolution: 38 µm, footprint: 2.38 cm), to characterize the musculotendinous system in vivo. This protocol allows for the identification of changes in muscle and tendon elasticities. Such innovative technological approaches have no equivalent to date, promise to accelerate our understanding of musculotendinous mechanical properties and have numerous research and clinical applications.

TGFbeta inducible early gene-1 knockout mice display defects in bone strength and microarchitecture.

TGFbeta inducible early gene-1 (TIEG) is a member of the Sp/Krüppel-like transcription factor family originally cloned from human osteoblasts. We have previously demonstrated that TIEG plays a role in the expression of important osteoblast marker genes and in the maturation/differentiation of osteoblasts. To elucidate the function of TIEG in skeletal development and maintenance, we have generated a TIEG knockout (KO) mouse. Three-point bending tests demonstrated that the femurs of TIEG KO mice are significantly weaker than those of wild-type animals. pQCT analysis of tibias revealed significant decreases in bone content, density and size in KO animals compared to wild-type mice. Micro-CT analysis of the femoral head and vertebrae revealed increases in femoral head trabecular separation and decreases in cortical bone thickness and vertebral bone volume in KO mice relative to wild-type controls. In addition, electron microscopy indicated a significant decrease in osteocyte number in the femurs of KO mice. Taken together, these data demonstrate that the bones of TIEG KO mice display an osteopenic phenotype with significantly weaker bones and reduced amounts of cortical and trabecular bone. In summary, an important role for TIEG in skeletal development and/or homeostasis is indicated.

Age-dependent changes in the mechanical properties of tail tendons in TGF-beta inducible early gene-1 knockout mice.

The purpose of this study is to investigate age-dependent changes in the architecture and mechanical properties of tendon in TGF-beta inducible early gene-1 (TIEG) knockout mice. Wild-type and TIEG knockout mice, aged 1, 2, and 15 mo, were used. The mechanical properties of tail tendons isolated from these mice were determined using uniaxial tensile ramp (0.05 mm/s) and relaxation (5 mm/s) tests, with a strain of 10%. Mechanical parameters (Young's modulus from the ramp test; fast and static stresses from the relaxation test) were measured and recorded. The structure of the tail tendon fascicle was characterized by transmission electron microscopy. The results of the mechanical testing revealed no significant difference between the knockout and wild-type groups at 1 or 15 mo of age. However, the fascicles of the knockout mice at 3 mo of age exhibited decreased fast and static stresses compared with those of the wild-type mice. Electron microscopy revealed an increase in fibril size in the knockout mouse tendons relative to wild-type controls at 1 and 3 mo of age. These data indicate an important role for TIEG in tendon microarchitecture and strength in adult mice.

Impact of TIEG1 Deletion on the Passive Mechanical Properties of Fast and Slow Twitch Skeletal Muscles in Female Mice.

As transforming growth factor (TGF)-ß inducible early gene-1 is highly expressed in skeletal muscle, the effect of TIEG1 gene deletion on the passive mechanical properties of slow and fast twitch muscle fibers was analyzed. Twenty five muscle fibers were harvested from soleus (Sol) and extensor digitorum longus (EDL) muscles from TIEG1-/- (N = 5) and control (N = 5) mice. Mechanical tests were performed on fibers and the dynamic and static stresses were measured. A viscoelastic Hill model of 3rd order was used to fit the experimental relaxation test data. In parallel, immunohistochemical analyses were performed on three serial transverse sections to detect the myosin isoforms within the slow and fast muscles. The percentage and the mean cross sectional area of each fiber type were calculated. These tests revealed a significant increase in the mechanical stress properties for the TIEG1-/- Sol fibers while a significant decrease appeared for the TIEG1-/- EDL fibers. Hill model tracked the shape of the experimental relaxation curve for both genotypes and both fiber types. Immunohistochemical results showed hypertrophy of all fiber types for TIEG1-/- muscles with an increase in the percentage of glycolytic fibers (IIX, and IIB) and a decrease of oxidative fibers (I, and IIA). This study has provided new insights into the role of TIEG1, known as KLF10, in the functional (SoltypeI: more resistant, EDLtypeIIB: less resistant) and morphological (glycolytic hypertrophy) properties of fast and slow twitch skeletal muscles. Further investigation at the cellular level will better reveal the role of the TIEG1 gene in skeletal muscle tissue.