Skeletal Muscle Pathology in X-Linked Myotubular Myopathy: Review With Cross-Species Comparisons

Michael W Lawlor; Alan H Beggs; Ana Buj-Bello; Martin K Childers; James J Dowling; Emma S James; Hui Meng; Steven A Moore; Suyash Prasad; Benedikt Schoser; Caroline A Sewry

doi:10.1093/jnen/nlv020

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Skeletal Muscle Pathology in X-Linked Myotubular Myopathy: Review With Cross-Species Comparisons

Journal article

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Peer reviewed

Skeletal Muscle Pathology in X-Linked Myotubular Myopathy: Review With Cross-Species Comparisons

Michael W Lawlor, Alan H Beggs, Ana Buj-Bello, Martin K Childers, James J Dowling, Emma S James, Hui Meng, Steven A Moore, Suyash Prasad, Benedikt Schoser, …

Journal of neuropathology and experimental neurology, Vol.75(2), pp.102-110

02/2016

DOI: 10.1093/jnen/nlv020

PMCID: PMC4765322

PMID: 26823526

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Abstract

X-linked myotubular myopathy (XLMTM) is a devastating, rare, congenital myopathy caused by mutations in the MTM1 gene, resulting in a lack of or dysfunction of the enzyme myotubularin. This leads to severe perinatal weakness and distinctive muscle pathology. It was originally thought that XLMTM was related to developmental arrest in myotube maturation; however, the generation and characterization of several animal models have significantly improved our understanding of clinical and pathological aspects of this disorder. Myotubularin is now known to participate in numerous cellular processes including endosomal trafficking, excitation-contraction coupling, cytoskeletal organization, neuromuscular junction structure, autophagy, and satellite cell proliferation and survival. The available vertebrate models of XLMTM, which vary in severity from complete absence to reduced functional levels of myotubularin, recapitulate features of the human disease to a variable extent. Understanding how pathological endpoints in animals with XLMTM translate to human patients will be essential to interpret preclinical treatment trials and translate therapies into human clinical studies. This review summarizes the published animal models of XLMTM, including those of zebrafish, mice, and dogs, with a focus on their pathological features as compared to those seen in human XLMTM patients.

Myotubular

Centronuclear

Congenital

Hypotrophy

Sarcotubular

Myopathy

Myotubularin

Details

Title: Subtitle: Skeletal Muscle Pathology in X-Linked Myotubular Myopathy: Review With Cross-Species Comparisons
Creators: Michael W Lawlor - From the Division of Pediatric Pathology, Department of Pathology and Laboratory Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin (MWL, HM); Division of Genetics and Genomics, The Manton Center for Orphan Disease Research, Boston Children’s Hospital, Harvard Medical School, Boston, Massachusetts (AHB); Genethon, INSERM U951, Evry, France (ABB); Department of Rehabilitation Medicine, University of Washington, Seattle, Washington (MKC); Division of Neurology, Department of Pediatrics, Hospital for Sick Children, Toronto, Ontario, Canada (JJD); Audentes Therapeutics, San Francisco, California (EJ, SP); The University of Iowa, Carver College of Medicine, Department of Pathology, Iowa City, Iowa (SAM); Friedrich-Baur-Institute, Department of Neurology, Ludwig-Maximilians-University Munich, Germany (BS); Dubowitz Neuromuscualar Centre, UCL Institute of Child Health/Great Ormond Street Hospital for Children, London, UK (CAS); and Wolfson Centre for Inherited Neuromuscular Diseases, RJAH Orthopaedic Hospital, Oswestry, UK (CAS)
Alan H Beggs - From the Division of Pediatric Pathology, Department of Pathology and Laboratory Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin (MWL, HM); Division of Genetics and Genomics, The Manton Center for Orphan Disease Research, Boston Children’s Hospital, Harvard Medical School, Boston, Massachusetts (AHB); Genethon, INSERM U951, Evry, France (ABB); Department of Rehabilitation Medicine, University of Washington, Seattle, Washington (MKC); Division of Neurology, Department of Pediatrics, Hospital for Sick Children, Toronto, Ontario, Canada (JJD); Audentes Therapeutics, San Francisco, California (EJ, SP); The University of Iowa, Carver College of Medicine, Department of Pathology, Iowa City, Iowa (SAM); Friedrich-Baur-Institute, Department of Neurology, Ludwig-Maximilians-University Munich, Germany (BS); Dubowitz Neuromuscualar Centre, UCL Institute of Child Health/Great Ormond Street Hospital for Children, London, UK (CAS); and Wolfson Centre for Inherited Neuromuscular Diseases, RJAH Orthopaedic Hospital, Oswestry, UK (CAS)
Ana Buj-Bello - From the Division of Pediatric Pathology, Department of Pathology and Laboratory Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin (MWL, HM); Division of Genetics and Genomics, The Manton Center for Orphan Disease Research, Boston Children’s Hospital, Harvard Medical School, Boston, Massachusetts (AHB); Genethon, INSERM U951, Evry, France (ABB); Department of Rehabilitation Medicine, University of Washington, Seattle, Washington (MKC); Division of Neurology, Department of Pediatrics, Hospital for Sick Children, Toronto, Ontario, Canada (JJD); Audentes Therapeutics, San Francisco, California (EJ, SP); The University of Iowa, Carver College of Medicine, Department of Pathology, Iowa City, Iowa (SAM); Friedrich-Baur-Institute, Department of Neurology, Ludwig-Maximilians-University Munich, Germany (BS); Dubowitz Neuromuscualar Centre, UCL Institute of Child Health/Great Ormond Street Hospital for Children, London, UK (CAS); and Wolfson Centre for Inherited Neuromuscular Diseases, RJAH Orthopaedic Hospital, Oswestry, UK (CAS)
Martin K Childers - From the Division of Pediatric Pathology, Department of Pathology and Laboratory Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin (MWL, HM); Division of Genetics and Genomics, The Manton Center for Orphan Disease Research, Boston Children’s Hospital, Harvard Medical School, Boston, Massachusetts (AHB); Genethon, INSERM U951, Evry, France (ABB); Department of Rehabilitation Medicine, University of Washington, Seattle, Washington (MKC); Division of Neurology, Department of Pediatrics, Hospital for Sick Children, Toronto, Ontario, Canada (JJD); Audentes Therapeutics, San Francisco, California (EJ, SP); The University of Iowa, Carver College of Medicine, Department of Pathology, Iowa City, Iowa (SAM); Friedrich-Baur-Institute, Department of Neurology, Ludwig-Maximilians-University Munich, Germany (BS); Dubowitz Neuromuscualar Centre, UCL Institute of Child Health/Great Ormond Street Hospital for Children, London, UK (CAS); and Wolfson Centre for Inherited Neuromuscular Diseases, RJAH Orthopaedic Hospital, Oswestry, UK (CAS)
James J Dowling - From the Division of Pediatric Pathology, Department of Pathology and Laboratory Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin (MWL, HM); Division of Genetics and Genomics, The Manton Center for Orphan Disease Research, Boston Children’s Hospital, Harvard Medical School, Boston, Massachusetts (AHB); Genethon, INSERM U951, Evry, France (ABB); Department of Rehabilitation Medicine, University of Washington, Seattle, Washington (MKC); Division of Neurology, Department of Pediatrics, Hospital for Sick Children, Toronto, Ontario, Canada (JJD); Audentes Therapeutics, San Francisco, California (EJ, SP); The University of Iowa, Carver College of Medicine, Department of Pathology, Iowa City, Iowa (SAM); Friedrich-Baur-Institute, Department of Neurology, Ludwig-Maximilians-University Munich, Germany (BS); Dubowitz Neuromuscualar Centre, UCL Institute of Child Health/Great Ormond Street Hospital for Children, London, UK (CAS); and Wolfson Centre for Inherited Neuromuscular Diseases, RJAH Orthopaedic Hospital, Oswestry, UK (CAS)
Emma S James - From the Division of Pediatric Pathology, Department of Pathology and Laboratory Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin (MWL, HM); Division of Genetics and Genomics, The Manton Center for Orphan Disease Research, Boston Children’s Hospital, Harvard Medical School, Boston, Massachusetts (AHB); Genethon, INSERM U951, Evry, France (ABB); Department of Rehabilitation Medicine, University of Washington, Seattle, Washington (MKC); Division of Neurology, Department of Pediatrics, Hospital for Sick Children, Toronto, Ontario, Canada (JJD); Audentes Therapeutics, San Francisco, California (EJ, SP); The University of Iowa, Carver College of Medicine, Department of Pathology, Iowa City, Iowa (SAM); Friedrich-Baur-Institute, Department of Neurology, Ludwig-Maximilians-University Munich, Germany (BS); Dubowitz Neuromuscualar Centre, UCL Institute of Child Health/Great Ormond Street Hospital for Children, London, UK (CAS); and Wolfson Centre for Inherited Neuromuscular Diseases, RJAH Orthopaedic Hospital, Oswestry, UK (CAS)
Hui Meng - From the Division of Pediatric Pathology, Department of Pathology and Laboratory Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin (MWL, HM); Division of Genetics and Genomics, The Manton Center for Orphan Disease Research, Boston Children’s Hospital, Harvard Medical School, Boston, Massachusetts (AHB); Genethon, INSERM U951, Evry, France (ABB); Department of Rehabilitation Medicine, University of Washington, Seattle, Washington (MKC); Division of Neurology, Department of Pediatrics, Hospital for Sick Children, Toronto, Ontario, Canada (JJD); Audentes Therapeutics, San Francisco, California (EJ, SP); The University of Iowa, Carver College of Medicine, Department of Pathology, Iowa City, Iowa (SAM); Friedrich-Baur-Institute, Department of Neurology, Ludwig-Maximilians-University Munich, Germany (BS); Dubowitz Neuromuscualar Centre, UCL Institute of Child Health/Great Ormond Street Hospital for Children, London, UK (CAS); and Wolfson Centre for Inherited Neuromuscular Diseases, RJAH Orthopaedic Hospital, Oswestry, UK (CAS)
Steven A Moore - From the Division of Pediatric Pathology, Department of Pathology and Laboratory Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin (MWL, HM); Division of Genetics and Genomics, The Manton Center for Orphan Disease Research, Boston Children’s Hospital, Harvard Medical School, Boston, Massachusetts (AHB); Genethon, INSERM U951, Evry, France (ABB); Department of Rehabilitation Medicine, University of Washington, Seattle, Washington (MKC); Division of Neurology, Department of Pediatrics, Hospital for Sick Children, Toronto, Ontario, Canada (JJD); Audentes Therapeutics, San Francisco, California (EJ, SP); The University of Iowa, Carver College of Medicine, Department of Pathology, Iowa City, Iowa (SAM); Friedrich-Baur-Institute, Department of Neurology, Ludwig-Maximilians-University Munich, Germany (BS); Dubowitz Neuromuscualar Centre, UCL Institute of Child Health/Great Ormond Street Hospital for Children, London, UK (CAS); and Wolfson Centre for Inherited Neuromuscular Diseases, RJAH Orthopaedic Hospital, Oswestry, UK (CAS)
Suyash Prasad - From the Division of Pediatric Pathology, Department of Pathology and Laboratory Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin (MWL, HM); Division of Genetics and Genomics, The Manton Center for Orphan Disease Research, Boston Children’s Hospital, Harvard Medical School, Boston, Massachusetts (AHB); Genethon, INSERM U951, Evry, France (ABB); Department of Rehabilitation Medicine, University of Washington, Seattle, Washington (MKC); Division of Neurology, Department of Pediatrics, Hospital for Sick Children, Toronto, Ontario, Canada (JJD); Audentes Therapeutics, San Francisco, California (EJ, SP); The University of Iowa, Carver College of Medicine, Department of Pathology, Iowa City, Iowa (SAM); Friedrich-Baur-Institute, Department of Neurology, Ludwig-Maximilians-University Munich, Germany (BS); Dubowitz Neuromuscualar Centre, UCL Institute of Child Health/Great Ormond Street Hospital for Children, London, UK (CAS); and Wolfson Centre for Inherited Neuromuscular Diseases, RJAH Orthopaedic Hospital, Oswestry, UK (CAS)
Benedikt Schoser - From the Division of Pediatric Pathology, Department of Pathology and Laboratory Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin (MWL, HM); Division of Genetics and Genomics, The Manton Center for Orphan Disease Research, Boston Children’s Hospital, Harvard Medical School, Boston, Massachusetts (AHB); Genethon, INSERM U951, Evry, France (ABB); Department of Rehabilitation Medicine, University of Washington, Seattle, Washington (MKC); Division of Neurology, Department of Pediatrics, Hospital for Sick Children, Toronto, Ontario, Canada (JJD); Audentes Therapeutics, San Francisco, California (EJ, SP); The University of Iowa, Carver College of Medicine, Department of Pathology, Iowa City, Iowa (SAM); Friedrich-Baur-Institute, Department of Neurology, Ludwig-Maximilians-University Munich, Germany (BS); Dubowitz Neuromuscualar Centre, UCL Institute of Child Health/Great Ormond Street Hospital for Children, London, UK (CAS); and Wolfson Centre for Inherited Neuromuscular Diseases, RJAH Orthopaedic Hospital, Oswestry, UK (CAS)
Caroline A Sewry - From the Division of Pediatric Pathology, Department of Pathology and Laboratory Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin (MWL, HM); Division of Genetics and Genomics, The Manton Center for Orphan Disease Research, Boston Children’s Hospital, Harvard Medical School, Boston, Massachusetts (AHB); Genethon, INSERM U951, Evry, France (ABB); Department of Rehabilitation Medicine, University of Washington, Seattle, Washington (MKC); Division of Neurology, Department of Pediatrics, Hospital for Sick Children, Toronto, Ontario, Canada (JJD); Audentes Therapeutics, San Francisco, California (EJ, SP); The University of Iowa, Carver College of Medicine, Department of Pathology, Iowa City, Iowa (SAM); Friedrich-Baur-Institute, Department of Neurology, Ludwig-Maximilians-University Munich, Germany (BS); Dubowitz Neuromuscualar Centre, UCL Institute of Child Health/Great Ormond Street Hospital for Children, London, UK (CAS); and Wolfson Centre for Inherited Neuromuscular Diseases, RJAH Orthopaedic Hospital, Oswestry, UK (CAS)
Resource Type: Journal article
Publication Details: Journal of neuropathology and experimental neurology, Vol.75(2), pp.102-110
DOI: 10.1093/jnen/nlv020
PMID: 26823526
PMCID: PMC4765322
NLM abbreviation: J Neuropathol Exp Neurol
ISSN: 0022-3069
eISSN: 1554-6578
Publisher: Oxford University Press
Language: English
Date published: 02/2016
Academic Unit: Pathology
Record Identifier: 9984047618602771

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