DOCSLIB.ORG

Generation and Characterization of a Dmdegfp Reporter Mouse As a Tool to Investigate Dystrophin Expression

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Generation and Characterization of a Dmdegfp Reporter Mouse As a Tool to Investigate Dystrophin Expression Generation and Characterization of a DmdEGFP Reporter Mouse as a Tool to Investigate Dystrophin Expression Inaugural-Dissertation to obtain the academic degree Doctor rerum naturalium (Dr. rer. nat.) Submitted to the Department of Biology, Chemistry and Pharmacy of the Freie Universität Berlin and in cotutelle to the Ecole Doctorale 515 "Complexité du vivant" of Université Pierre et Marie Curie Paris by Mina Petkova from Sofia, Bulgaria 2015 The research presented in this thesis was conducted from October 2011 until December 2015 in the followng laboratories: Department of neuropediatrics and NeuroCure, Charité Cross Over, Charité Universitätmedizin, Berlin, Germany. Biothérapies des maladies neuromusculaires, UFR des sciences de la santé Simone Veil, Université de Versailles Saint-Quentin-en-Yvelines, France. THESIS COMMITTEE: Thesis supervisor and reviewer Freie Universität Berlin: Prof. Dr. Markus Schuelke Thesis supervisor Université Pierre et Marie Curie Paris: Prof. Dr. Helge Amthor Representative Université Pierre et Marie Curie Paris: Dr. Gillian Butler-Browne Reviewer Freie Universität Berlin: Prof. Dr. Sigmar Stricker External reviewer: Prof. Dr. Volker Straub External reviewer: Prof. Dr. Ketan Patel Postdoctoral fellow Freie Universität Berlin: Dr. Annemarie Hofmann Date of defense: 05.02.2016 STATUTORY DECLARATION I hereby declare that I wrote the presented dissertation “Generation and characterization of a DmdEGFP reporter mouse as a tool to investigate dystrophin expression” independently and used no other aids than those cited. In the written paragraphs, I have clearly identified the source of the passages that are quoted or paraphrased from other works. I also hereby declare that I have conducted my scientific work according to the principles of good scientific practice in accordance with the current “Richtlinien der Freien Universität Berlin” (Guidelines of the Free University of Berlin) and “Charte du doctorat à l’UPMC” (Charter of PhD students at UPMC). I, Mina Petkova, received assistance in the writing of this thesis with respect to grammar and syntax, which was provided by Markus Schuelke and Helge Amthor. Berlin, 6.01.2016 _______________ (Signature) ACKNOWLEDGMENTS I would like to cordially thank all whose support and encouragement contributed to the successful completion of my doctoral thesis. First of all, I would like to thank my supervisors Prof. Dr. M. Schuelke and Prof. Dr. H. Amthor for giving me the opportunity to work on an exciting project over the past 4.5 years. I will always appreciate their scientific advice and their work ethics. I am very grateful to Prof. Dr. M. Schuelke for his generosity, his unconditional support, his guidance and for giving me the freedom to conduct research. His interest and passion in the field of the biomedical research, and his optimism always encouraged me and contributed to the success of my work. I would like to cordially thank Prof. Dr. S. Stricker of the Freie Universitat Berlin for his agreement to review my doctoral thesis. I would like to cordially thank Prof. Dr. V. Straub and Prof. Dr. K. Patel for their willingness to review my doctoral thesis. I thank Dr. G. Butler-Browne for agreeing to be part of my thesis committee. I would like to express special thanks to all current and former co-workers of the Schuelke group in Berlin for their help, understanding, for their encouragment, and for the friendly and nice work atmosphere. I would especially like to thank Susanne, Esther and Franziska for their technical assistance. I am very thankful to Can for her unconditional support, great discussions, understanding and friendship. I am grateful to Evelyn and Sophie, students who helped and supported my project. I would also like to thank the members of the group of Prof. Dr. H. Amthor and Dr. L. Garcia at the Université Saint-Quentin en Yvelines, especially to Amalia and Sonia. I also would like to thank Josefine Radke and co-workers at the Institute of Neuropathology at the Charité Universitätsmedizin, Berlin for performing the histological analysis and western blots. I would like to thank Polygene AG, Switzerland for the generation of the transgenic mice. I am thankful to the group of Prof. Dr. Carmen Birchmeier from MDC-Berlin for providing the Cre-deleter mice. I want to thank to all co-workers of the animal facilities of the Charité Cross Over building, as well as in the central animal facility FEM in Berlin for caring and breeding of experimental animals. I would like to thank MyoGrad for giving me the opportunity to be part of a bi-national PhD program. Thanks to all students and to the organization team, especially Susanne Wissler. I would like to thank my family, especially my parents and my grandmother for their love, for their support each step of the way, for giving me the chance to explore different opportunities, and ultimately to achieve this important goal. Finally, I would like to thank all my friends for their patience, support, for believing in me and for the energy they gave me to accomplish my work. The most beautiful thing we can experience is the mysterious. It is the source of all true art and science. (Albert Einstein) TABLE OF CONTENTS TABLE OF CONTENTS 1. Summary ................................................................................................................... 1 2. Zusammenfassung ..................................................................................................... 2 3. Résumé ..................................................................................................................... 4 4. Introduction .............................................................................................................. 6 4.1. Pathology of Duchenne muscular dystrophy ....................................................... 6 4.2. The mdx mouse: a naturally occurring animal model for DMD ............................ 8 4.3. The structure and function of the muscle ........................................................... 9 4.3.1. Skeletal muscle ....................................................................................................... 9 4.3.2. Cardiac and smooth muscle ................................................................................. 11 4.3.3. Myogenesis ........................................................................................................... 12 4.3.4. The satellite cell and skeletal muscle regeneration ............................................. 12 4.4. Dystrophin ....................................................................................................... 14 4.4.1. The DMD gene ...................................................................................................... 14 4.4.2. The dystrophin protein in the skeletal muscle ..................................................... 16 4.4.3. Dystrophin associated protein complex (DAPC) .................................................. 18 4.4.4. Utrophin: a dystrophin homolog .......................................................................... 21 4.4.5. Dystrophin in cardiac and smooth muscles ......................................................... 22 4.4.6. Dystrophin in non-muscle tissues ........................................................................ 24 4.4.7. The role of dystrophin in satellite cells ................................................................ 28 4.5. Mutations of the DMD gene ............................................................................. 29 4.6. Revertant fibers in DMD patients and in mdx mice ........................................... 30 4.7. Therapies for DMD ........................................................................................... 31 4.8. Aims of the study ............................................................................................. 33 5. Materials ................................................................................................................. 36 5.1. Plastic materials ............................................................................................... 36 5.2. Instruments, equipment................................................................................... 37 5.3. Chemicals ........................................................................................................ 38 5.4. Kit systems, markers, enzymes and nucleotides................................................ 40 5.5. Plasmids .......................................................................................................... 41 5.6. Bacteria ........................................................................................................... 41 5.7. Antibodies ....................................................................................................... 41 5.8. Oligonucleotide primers for PCR....................................................................... 41 5.9. Cell lines .......................................................................................................... 42 5.10. Animal experiments ......................................................................................... 42 i 5.11. Software .......................................................................................................... 42 6. Methods ................................................................................................................. 44 6.1. Methods for the generation of a transgenic Dystrophin-EGFP reporter mouse .. 44 6.2. Generation of the
Load more

Recommended publications
  • Microanatomy of Muscles
    Microanatomy of Muscles Anatomy & Physiology Class Three Main Muscle Types Objectives: By the end of this presentation you will have the information to: 1. Describe the 3 main types of muscles. 2. Detail the functions of the muscle system. 3. Correctly label the parts of a myocyte (muscle cell) 4. Identify the levels of organization in a skeletal muscle from organ to myosin. 5. Explain how a muscle contracts utilizing the correct terminology of the sliding filament theory. 6. Contrast and compare cardiac and smooth muscle with skeletal muscle. Major Functions: Muscle System 1. Moving the skeletal system and posture. 2. Passing food through the digestive system & constriction of other internal organs. 3. Production of body heat. 4. Pumping the blood throughout the body. 5. Communication - writing and verbal Specialized Cells (Myocytes) ~ Contractile Cells Can shorten along one or more planes because of specialized cell membrane (sarcolemma) and specialized cytoskeleton. Specialized Structures found in Myocytes Sarcolemma: The cell membrane of a muscle cell Transverse tubule: a tubular invagination of the sarcolemma of skeletal or cardiac muscle fibers that surrounds myofibrils; involved in transmitting the action potential from the sarcolemma to the interior of the myofibril. Sarcoplasmic Reticulum: The special type of smooth endoplasmic Myofibrils: reticulum found in smooth and a contractile fibril of skeletal muscle, composed striated muscle fibers whose function mainly of actin and myosin is to store and release calcium ions. Multiple Nuclei (skeletal) & many mitochondria Skeletal Muscle - Microscopic Anatomy A whole skeletal muscle (such as the biceps brachii) is considered an organ of the muscular system. Each organ consists of skeletal muscle tissue, connective tissue, nerve tissue, and blood or vascular tissue.
    [Show full text]
  • Development of a High-Throughput Screen to Identify Small Molecule Enhancers of Sarcospan for the Treatment of Duchenne Muscular Dystrophy
    UCLA UCLA Previously Published Works Title Development of a high-throughput screen to identify small molecule enhancers of sarcospan for the treatment of Duchenne muscular dystrophy. Permalink https://escholarship.org/uc/item/85z6k8t7 Journal Skeletal muscle, 9(1) ISSN 2044-5040 Authors Shu, Cynthia Kaxon-Rupp, Ariana N Collado, Judd R et al. Publication Date 2019-12-12 DOI 10.1186/s13395-019-0218-x Peer reviewed eScholarship.org Powered by the California Digital Library University of California Shu et al. Skeletal Muscle (2019) 9:32 https://doi.org/10.1186/s13395-019-0218-x RESEARCH Open Access Development of a high-throughput screen to identify small molecule enhancers of sarcospan for the treatment of Duchenne muscular dystrophy Cynthia Shu1,2,3, Ariana N. Kaxon-Rupp2, Judd R. Collado2, Robert Damoiseaux4,5 and Rachelle H. Crosbie1,2,3,6* Abstract Background: Duchenne muscular dystrophy (DMD) is caused by loss of sarcolemma connection to the extracellular matrix. Transgenic overexpression of the transmembrane protein sarcospan (SSPN) in the DMD mdx mouse model significantly reduces disease pathology by restoring membrane adhesion. Identifying SSPN-based therapies has the potential to benefit patients with DMD and other forms of muscular dystrophies caused by deficits in muscle cell adhesion. Methods: Standard cloning methods were used to generate C2C12 myoblasts stably transfected with a fluorescence reporter for human SSPN promoter activity. Assay development and screening were performed in a core facility using liquid handlers and imaging systems specialized for use with a 384-well microplate format. Drug-treated cells were analyzed for target gene expression using quantitative PCR and target protein expression using immunoblotting.
    [Show full text]
  • Muscle Physiology Dr
    Muscle Physiology Dr. Ebneshahidi Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Skeletal Muscle Figure 9.2 (a) Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Functions of the muscular system . 1. Locomotion . 2. Vasoconstriction and vasodilatation- constriction and dilation of blood vessel Walls are the results of smooth muscle contraction. 3. Peristalsis – wavelike motion along the digestive tract is produced by the Smooth muscle. 4. Cardiac motion . 5. Posture maintenance- contraction of skeletal muscles maintains body posture and muscle tone. 6. Heat generation – about 75% of ATP energy used in muscle contraction is released as heat. Copyright. © 2004 Pearson Education, Inc., publishing as Benjamin Cummings . Striation: only present in skeletal and cardiac muscles. Absent in smooth muscle. Nucleus: smooth and cardiac muscles are uninculcated (one nucleus per cell), skeletal muscle is multinucleated (several nuclei per cell ). Transverse tubule ( T tubule ): well developed in skeletal and cardiac muscles to transport calcium. Absent in smooth muscle. Intercalated disk: specialized intercellular junction that only occurs in cardiac muscle. Control: skeletal muscle is always under voluntary control‚ with some exceptions ( the tongue and pili arrector muscles in the dermis). smooth and cardiac muscles are under involuntary control. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Innervation: motor unit . a) a motor nerve and a myofibril from a neuromuscular junction where gap (called synapse) occurs between the two structures. at the end of motor nerve‚ neurotransmitter (i.e. acetylcholine) is stored in synaptic vesicles which will release the neurotransmitter using exocytosis upon the stimulation of a nerve impulse. Across the synapse the surface the of myofibril contains receptors that can bind with the neurotransmitter.
    [Show full text]
  • Dystrophin Complex Functions As a Scaffold for Signalling Proteins☆
    View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Elsevier - Publisher Connector Biochimica et Biophysica Acta 1838 (2014) 635–642 Contents lists available at ScienceDirect Biochimica et Biophysica Acta journal homepage: www.elsevier.com/locate/bbamem Review Dystrophin complex functions as a scaffold for signalling proteins☆ Bruno Constantin IPBC, CNRS/Université de Poitiers, FRE 3511, 1 rue Georges Bonnet, PBS, 86022 Poitiers, France article info abstract Article history: Dystrophin is a 427 kDa sub-membrane cytoskeletal protein, associated with the inner surface membrane and Received 27 May 2013 incorporated in a large macromolecular complex of proteins, the dystrophin-associated protein complex Received in revised form 22 August 2013 (DAPC). In addition to dystrophin the DAPC is composed of dystroglycans, sarcoglycans, sarcospan, dystrobrevins Accepted 28 August 2013 and syntrophin. This complex is thought to play a structural role in ensuring membrane stability and force trans- Available online 7 September 2013 duction during muscle contraction. The multiple binding sites and domains present in the DAPC confer the scaf- fold of various signalling and channel proteins, which may implicate the DAPC in regulation of signalling Keywords: Dystrophin-associated protein complex (DAPC) processes. The DAPC is thought for instance to anchor a variety of signalling molecules near their sites of action. syntrophin The dystroglycan complex may participate in the transduction of extracellular-mediated signals to the muscle Sodium channel cytoskeleton, and β-dystroglycan was shown to be involved in MAPK and Rac1 small GTPase signalling. More TRPC channel generally, dystroglycan is view as a cell surface receptor for extracellular matrix proteins.
    [Show full text]
  • Dystrobrevin Alpha Gene Is a Direct Target of the Vitamin D Receptor in Muscle
    64 3 Journal of Molecular M K Tsoumpra et al. Upregulation of dystrobrevin by 64:3 195–208 Endocrinology calcitriol RESEARCH Dystrobrevin alpha gene is a direct target of the vitamin D receptor in muscle Maria K Tsoumpra1, Shun Sawatsubashi2, Michihiro Imamura1, Seiji Fukumoto2, Shin’ichi Takeda1, Toshio Matsumoto2 and Yoshitsugu Aoki1 1Department of Molecular Therapy, National Institute of Neuroscience, National Centre of Neurology and Psychiatry, Tokyo, Japan 2Fujii Memorial Institute of Medical Sciences, Tokushima University, Tokushima, Japan Correspondence should be addressed to S Fukumoto: [email protected] Abstract The biologically active metabolite of vitamin D, 1,25-dihydroxyvitamin D3 (VD3), exerts its Key Words tissue-specific actions through binding to its intracellular vitamin D receptor (VDR) which f vitamin D functions as a heterodimer with retinoid X receptor (RXR) to recognize vitamin D response f muscle elements (VDRE) and activate target genes. Upregulation of VDR in murine skeletal muscle f gene regulation cells occurs concomitantly with transcriptional regulation of key myogenic factors upon f receptor binding VD3 administration, reinforcing the notion that VD3 exerts beneficial effects on muscle. Herein we elucidated the regulatory role of VD3/VDR axis on the expression of dystrobrevin alpha (DTNA), a member of dystrophin-associated protein complex (DAPC). In C2C12 cells, Dtna and VDR gene and protein expression were upregulated by 1–50 nM of VD3 during all stages of myogenic differentiation. In the dystrophic-derived H2K-mdx52 cells, upregulation of DTNA by VD3 occurred upon co-transfection of VDR and RXR expression vectors. Silencing of MyoD1, an E-box binding myogenic transcription factor, did not alter the VD3-mediated Dtna induction, but Vdr silencing abolished this effect.
    [Show full text]
  • Reviewreview Duchenne Muscular Dystrophy and Dystrophin: Pathogenesis and Opportunities for Treatment Third in Molecular Medicine Review Series Kristen J
    reviewreview Duchenne muscular dystrophy and dystrophin: pathogenesis and opportunities for treatment Third in Molecular Medicine Review Series Kristen J. Nowak† & Kay E. Davies+ MRC Functional Genetics Unit, University of Oxford, UK Duchenne muscular dystrophy (DMD) is caused by mutations in protein. Becker muscular dystrophy (BMD; OMIM 300376)—a the gene that encodes the 427-kDa cytoskeletal protein dys- much milder form of the disease—is caused by a reduction in the trophin. Increased knowledge of the function of dystrophin and amount, or alteration in the size, of the dystrophin protein. The its role in muscle has led to a greater understanding of the high incidence of sporadic cases of DMD (1 in 10,000 sperm or pathogenesis of DMD. This, together with advances in the eggs) means that genetic screening will never eliminate this dis- genetic toolkit of the molecular biologist, are leading to many ease, so an effective therapy is highly desirable. This review sum- different approaches to treatment. Gene therapy can be marizes our understanding of the disease and the strategies that are achieved using plasmids or viruses, mutations can be corrected being developed for an effective treatment (Fig 1). using chimaeraplasts and short DNA fragments, exon skipping of mutations can be induced using oligonucleotides and Pathogenesis readthrough of nonsense mutations can be achieved using Dystrophin has a major structural role in muscle as it links the aminoglycoside antibiotics. Blocking the proteasome degrada- internal cytoskeleton to the extracellular matrix. The amino-terminus tion pathway can stabilize any truncated dystrophin protein, of dystrophin binds to F-actin and the carboxyl terminus to the and upregulation of other proteins can also prevent the dys- dystrophin-associated protein complex (DAPC) at the sarcolemma trophic process.
    [Show full text]
  • Governs the Making of Photocopies Or Other Reproductions of Copyrighted Materials
    Warning Concerning Copyright Restrictions The Copyright Law of the United States (Title 17, United States Code) governs the making of photocopies or other reproductions of copyrighted materials. Under certain conditions specified in the law, libraries and archives are authorized to furnish a photocopy or other reproduction. One of these specified conditions is that the photocopy or reproduction is not to be used for any purpose other than private study, scholarship, or research. If electronic transmission of reserve material is used for purposes in excess of what constitutes "fair use," that user may be liable for copyright infringement. University of Nevada, Reno The Role of Utrophin, Sarcospan, and Glycosyltransferase Activity in the Pathogenesis of Duchenne Muscular Dystrophy and a Representative Case Study A thesis submitted in partial fulfillment of the requirements for the degree of Bachelor of Science in Biochemistry & Molecular Biology by Susan T. Alaei Josh Baker, Ph.D., Thesis Advisor May, 2013 UNIVERSITY OF NEVADA THE HONORS PROGRAM RENO We recommend that the thesis prepared under our supervision by Susan T. Alaei entitled The Role of Utrophin, Sarcospan, and Glycosyltransferase Activity in the Pathogenesis of Duchenne Muscular Dystrophy and a Representative Case Study be accepted in partial fulfillment of the requirements for the degree of Bachelor of Science in Biochemistry & Molecular Biology ______________________________________________ Josh Baker, Ph.D., Thesis Advisor ______________________________________________ Tamara Valentine, Ph.D., Director, Honors Program May 2013 i Abstract Duchenne Muscular Dystrophy is a degenerative muscle disease that is characterized by the breakdown of skeletal muscle as a result of membrane instability. A mutation in the dystrophin gene, one of the largest gene in the human genome, results in a complete lack of dystrophin in the membrane of skeletal muscle cells.
    [Show full text]
  • Sarcospan-Dependent Akt Activation Is Required for Utrophin Expression and Muscle Regeneration
    JCB: Article Sarcospan-dependent Akt activation is required for utrophin expression and muscle regeneration Jamie L. Marshall,1 Johan Holmberg,1 Eric Chou,1 Amber C. Ocampo,1 Jennifer Oh,1 Joy Lee,1 Angela K. Peter,1 Paul T. Martin,3,4 and Rachelle H. Crosbie-Watson1,2 1Department of Integrative Biology and Physiology and 2Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA 90095 3Center for Gene Therapy, The Research Institute, Nationwide Children’s Hospital, and 4Department of Pediatrics, Ohio State University College of Medicine and College of Public Health, Columbus, OH 43205 trophin is normally confined to the neuromus- sarcolemma. SSPN-null mice displayed delayed differen- cular junction (NMJ) in adult muscle and par- tiation after CTX injury caused by loss of utrophin and Akt U tially compensates for the loss of dystrophin in signaling. Treatment of SSPN-null mice with viral Akt mdx mice. We show that Akt signaling and utrophin increased utrophin and restored muscle repair after in- levels were diminished in sarcospan (SSPN)-deficient jury, revealing an important role for the SSPN-Akt-utro- muscle. By creating several transgenic and knockout phin signaling axis in regeneration. SSPN improved cell mice, we demonstrate that SSPN regulates Akt signal- surface expression of utrophin by increasing transportation ing to control utrophin expression. SSPN determined of utrophin and DG from endoplasmic reticulum/Golgi -dystroglycan (-DG) glycosylation by affecting levels membranes. Our experiments reveal functions of utro- of the NMJ-specific glycosyltransferase Galgt2. After phin in regeneration and new pathways that regulate cardiotoxin (CTX) injury, regenerating myofibers ex- utrophin expression at the cell surface.
    [Show full text]
  • Titin Force Is Enhanced in Actively Stretched Skeletal Muscle
    © 2014. Published by The Company of Biologists Ltd | The Journal of Experimental Biology (2014) 217, 3629-3636 doi:10.1242/jeb.105361 RESEARCH ARTICLE Titin force is enhanced in actively stretched skeletal muscle Krysta Powers1, Gudrun Schappacher-Tilp2, Azim Jinha1, Tim Leonard1, Kiisa Nishikawa3 and Walter Herzog1,* ABSTRACT Aubert, 1952; Edman et al., 1978; Edman et al., 1982; Morgan, 1994; The sliding filament theory of muscle contraction is widely accepted Herzog et al., 2006; Leonard and Herzog, 2010). This property, as the means by which muscles generate force during activation. termed residual force enhancement, provides a direct challenge to the Within the constraints of this theory, isometric, steady-state force sliding filament-based cross-bridge theory. produced during muscle activation is proportional to the amount of Residual force enhancement has been observed in vivo and down filament overlap. Previous studies from our laboratory demonstrated to the sarcomere level (Abbott and Aubert, 1952; Edman et al., enhanced titin-based force in myofibrils that were actively stretched 1982; Herzog and Leonard, 2002; Leonard et al., 2010; Rassier, to lengths which exceeded filament overlap. This observation cannot 2012). There are three main filaments at the sarcomere level that be explained by the sliding filament theory. The aim of the present contribute to force production in muscle: the thick (myosin), the thin study was to further investigate the enhanced state of titin during (actin), and the titin filaments. The thick filament is composed active stretch. Specifically, we confirm that this enhanced state of primarily of the protein myosin, and the thin filament is composed force is observed in a mouse model and quantify the contribution of of actin and regulatory proteins.
    [Show full text]
  • Biomechanics of Skeletal Muscle
    BiomechanicsBiomechanics ofof SkeletalSkeletal MuscleMuscle www.fisiokinesiterapia.biz ContentsContents I.I. CompositionComposition && structurestructure ofof skeletalskeletal musclemuscle II.II. MechanicsMechanics ofof MuscleMuscle ContractionContraction III.III. ForceForce productionproduction inin musclemuscle IV.IV. MuscleMuscle remodelingremodeling V.V. SummarySummary 2 MuscleMuscle types:types: –– cardiaccardiac muscle:muscle: composescomposes thethe heartheart –– smoothsmooth muscle:muscle: lineslines hollowhollow internalinternal organsorgans –– skeletalskeletal (striated(striated oror voluntary)voluntary) muscle:muscle: attachedattached toto skeletonskeleton viavia tendontendon && movementmovement SkeletalSkeletal musclemuscle 4040--45%45% ofof bodybody weightweight –– >> 430430 musclesmuscles –– ~~ 8080 pairspairs produceproduce vigorousvigorous movementmovement DynamicDynamic && staticstatic workwork –– Dynamic:Dynamic: locomotionlocomotion && positioningpositioning ofof segmentssegments –– Static:Static: maintainsmaintains bodybody postureposture 3 I.I. CompositionComposition && structurestructure ofof skeletalskeletal musclemuscle Structure & organization • Muscle fiber: long cylindrical multi-nuclei cell 10-100 μm φ fiber →endomysium → fascicles → perimysium → epimysium (fascia) • Collagen fibers in perimysium & epimysium are continuous with those in tendons • {thin filament (actin 5nm φ) + thick filament (myosin 15 nm φ )} → myofibrils (contractile elements, 1μm φ) →muscle fiber 4 5 6 BandsBands ofof myofibrilsmyofibrils
    [Show full text]
  • Skeletal Muscle Tissue and Muscle Organization
    Chapter 9 The Muscular System Skeletal Muscle Tissue and Muscle Organization Lecture Presentation by Steven Bassett Southeast Community College © 2015 Pearson Education, Inc. Introduction • Humans rely on muscles for: • Many of our physiological processes • Virtually all our dynamic interactions with the environment • Skeletal muscles consist of: • Elongated cells called fibers (muscle fibers) • These fibers contract along their longitudinal axis © 2015 Pearson Education, Inc. Introduction • There are three types of muscle tissue • Skeletal muscle • Pulls on skeletal bones • Voluntary contraction • Cardiac muscle • Pushes blood through arteries and veins • Rhythmic contractions • Smooth muscle • Pushes fluids and solids along the digestive tract, for example • Involuntary contraction © 2015 Pearson Education, Inc. Introduction • Muscle tissues share four basic properties • Excitability • The ability to respond to stimuli • Contractility • The ability to shorten and exert a pull or tension • Extensibility • The ability to continue to contract over a range of resting lengths • Elasticity • The ability to rebound toward its original length © 2015 Pearson Education, Inc. Functions of Skeletal Muscles • Skeletal muscles perform the following functions: • Produce skeletal movement • Pull on tendons to move the bones • Maintain posture and body position • Stabilize the joints to aid in posture • Support soft tissue • Support the weight of the visceral organs © 2015 Pearson Education, Inc. Functions of Skeletal Muscles • Skeletal muscles perform
    [Show full text]
  • Muscle Diseases: the Muscular Dystrophies
    ANRV295-PM02-04 ARI 13 December 2006 2:57 Muscle Diseases: The Muscular Dystrophies Elizabeth M. McNally and Peter Pytel Department of Medicine, Section of Cardiology, University of Chicago, Chicago, Illinois 60637; email: [email protected] Department of Pathology, University of Chicago, Chicago, Illinois 60637; email: [email protected] Annu. Rev. Pathol. Mech. Dis. 2007. Key Words 2:87–109 myotonia, sarcopenia, muscle regeneration, dystrophin, lamin A/C, The Annual Review of Pathology: Mechanisms of Disease is online at nucleotide repeat expansion pathmechdis.annualreviews.org Abstract by Drexel University on 01/13/13. For personal use only. This article’s doi: 10.1146/annurev.pathol.2.010506.091936 Dystrophic muscle disease can occur at any age. Early- or childhood- onset muscular dystrophies may be associated with profound loss Copyright c 2007 by Annual Reviews. All rights reserved of muscle function, affecting ambulation, posture, and cardiac and respiratory function. Late-onset muscular dystrophies or myopathies 1553-4006/07/0228-0087$20.00 Annu. Rev. Pathol. Mech. Dis. 2007.2:87-109. Downloaded from www.annualreviews.org may be mild and associated with slight weakness and an inability to increase muscle mass. The phenotype of muscular dystrophy is an endpoint that arises from a diverse set of genetic pathways. Genes associated with muscular dystrophies encode proteins of the plasma membrane and extracellular matrix, and the sarcomere and Z band, as well as nuclear membrane components. Because muscle has such distinctive structural and regenerative properties, many of the genes implicated in these disorders target pathways unique to muscle or more highly expressed in muscle.
    [Show full text]