The Effects of Low Levels of Dystrophin on Mouse Muscle Function and Pathology
Publication Date
February 16, 2012
Journal
PLOS ONE
Authors
Maaike Van Putten, Margriet Hulsker, Vishna Devi Nadarajah, Sandra H. Van Heiningen, et al
Volume
7
Issue
2
Pages
e31937
DOI
https://dx.plos.org/10.1371/journal.pone.0031937
Publisher URL
http://journals.plos.org/plosone/article?id=10.1371%2Fjournal.pone.0031937
PubMed
http://www.ncbi.nlm.nih.gov/pubmed/22359642
PubMed Central
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3281102
Europe PMC
http://europepmc.org/abstract/MED/22359642
Web of Science
000302796200111
Scopus
84857126451
Mendeley
http://www.mendeley.com/research/effects-low-levels-dystrophin-mouse-muscle-function-pathology
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Mendeley | Further Information

{"title"=>"The effects of low levels of dystrophin on mouse muscle function and pathology", "type"=>"journal", "authors"=>[{"first_name"=>"Maaike", "last_name"=>"van Putten", "scopus_author_id"=>"36341531200"}, {"first_name"=>"Margriet", "last_name"=>"Hulsker", "scopus_author_id"=>"36716207700"}, {"first_name"=>"Vishna Devi", "last_name"=>"Nadarajah", "scopus_author_id"=>"14048599600"}, {"first_name"=>"Sandra H.", "last_name"=>"van Heiningen", "scopus_author_id"=>"26026535100"}, {"first_name"=>"Ella", "last_name"=>"van Huizen", "scopus_author_id"=>"54997948500"}, {"first_name"=>"Maarten", "last_name"=>"van Iterson", "scopus_author_id"=>"35108194600"}, {"first_name"=>"Peter", "last_name"=>"Admiraal", "scopus_author_id"=>"54913913600"}, {"first_name"=>"Tobias", "last_name"=>"Messemaker", "scopus_author_id"=>"54997948200"}, {"first_name"=>"Johan T.", "last_name"=>"den Dunnen", "scopus_author_id"=>"7005591386"}, {"first_name"=>"Peter A C", "last_name"=>"'t Hoen", "scopus_author_id"=>"55909479400"}, {"first_name"=>"Annemieke", "last_name"=>"Aartsma-Rus", "scopus_author_id"=>"6506555410"}], "year"=>2012, "source"=>"PLoS ONE", "identifiers"=>{"issn"=>"19326203", "isbn"=>"1932-6203 (Electronic)\\r1932-6203 (Linking)", "pui"=>"364271832", "sgr"=>"84857126451", "doi"=>"10.1371/journal.pone.0031937", "scopus"=>"2-s2.0-84857126451", "pmid"=>"22359642"}, "id"=>"0f43daec-bcc3-3d1d-a32e-aa30993ab244", "abstract"=>"Duchenne muscular dystrophy (DMD) is a severe progressive muscular disorder caused by reading frame disrupting mutations in the DMD gene, preventing the synthesis of functional dystrophin. As dystrophin provides muscle fiber stability during contractions, dystrophin negative fibers are prone to exercise-induced damage. Upon exhaustion of the regenerative capacity, fibers will be replaced by fibrotic and fat tissue resulting in a progressive loss of function eventually leading to death in the early thirties. With several promising approaches for the treatment of DMD aiming at dystrophin restoration in clinical trials, there is an increasing need to determine more precisely which dystrophin levels are sufficient to restore muscle fiber integrity, protect against muscle damage and improve muscle function.To address this we generated a new mouse model (mdx-Xist(Δhs)) with varying, low dystrophin levels (3-47%, mean 22.7%, stdev 12.1, n = 24) due to skewed X-inactivation. Longitudinal sections revealed that within individual fibers, some nuclei did and some did not express dystrophin, resulting in a random, mosaic pattern of dystrophin expression within fibers.Mdx-Xist(Δhs), mdx and wild type females underwent a 12 week functional test regime consisting of different tests to assess muscle function at base line, or after chronic treadmill running exercise. Overall, mdx-Xist(Δhs) mice with 3-14% dystrophin outperformed mdx mice in the functional tests. Improved histopathology was observed in mice with 15-29% dystrophin and these levels also resulted in normalized expression of pro-inflammatory biomarker genes, while for other parameters >30% of dystrophin was needed. Chronic exercise clearly worsened pathology, which needed dystrophin levels >20% for protection. Based on these findings, we conclude that while even dystrophin levels below 15% can improve pathology and performance, levels of >20% are needed to fully protect muscle fibers from exercise-induced damage.", "link"=>"http://www.mendeley.com/research/effects-low-levels-dystrophin-mouse-muscle-function-pathology", "reader_count"=>55, "reader_count_by_academic_status"=>{"Librarian"=>2, "Researcher"=>11, "Student > Doctoral Student"=>2, "Student > Ph. D. Student"=>13, "Student > Postgraduate"=>4, "Student > Master"=>10, "Other"=>2, "Student > Bachelor"=>7, "Lecturer"=>1, "Professor"=>3}, "reader_count_by_user_role"=>{"Librarian"=>2, "Researcher"=>11, "Student > Doctoral Student"=>2, "Student > Ph. D. Student"=>13, "Student > Postgraduate"=>4, "Student > Master"=>10, "Other"=>2, "Student > Bachelor"=>7, "Lecturer"=>1, "Professor"=>3}, "reader_count_by_subject_area"=>{"Engineering"=>1, "Biochemistry, Genetics and Molecular Biology"=>9, "Agricultural and Biological Sciences"=>28, "Medicine and Dentistry"=>12, "Neuroscience"=>2, "Sports and Recreations"=>1, "Pharmacology, Toxicology and Pharmaceutical Science"=>1, "Social Sciences"=>1}, "reader_count_by_subdiscipline"=>{"Engineering"=>{"Engineering"=>1}, "Medicine and Dentistry"=>{"Medicine and Dentistry"=>12}, "Neuroscience"=>{"Neuroscience"=>2}, "Social Sciences"=>{"Social Sciences"=>1}, "Sports and Recreations"=>{"Sports and Recreations"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>28}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>9}, "Pharmacology, Toxicology and Pharmaceutical Science"=>{"Pharmacology, Toxicology and Pharmaceutical Science"=>1}}, "reader_count_by_country"=>{"Canada"=>1, "Netherlands"=>1, "Romania"=>1, "United States"=>1, "Japan"=>1, "Germany"=>1}, "group_count"=>3}

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Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/682431"], "description"=>"<p>A. Normalization towards wild type levels was observed for bodyweight of the <i>mdx-Xist</i><sup>Δhs</sup> mice. At the end of the functional test regime <i>mdx</i> mice were significantly heavier (<i>P</i><0.001) than the other mice. B. CK levels of <i>mdx</i> and <i>mdx-Xist</i><sup>Δhs</sup> mice with low dystrophin levels were both significantly (<i>P</i><0.001) higher compared to the levels of <i>mdx-Xist</i><sup>Δhs</sup> mice with >30% dystrophin and <i>Xist</i><sup>Δhs</sup> mice. C. Four limb hanging wire performance was comparable for the <i>Xist</i><sup>Δhs</sup> and <i>mdx-Xist</i><sup>Δhs</sup> mice, while <i>mdx</i> mice performed significantly (<i>P</i><0.001) worse. D. The best performance on the two limb hanging wire test was obtained for the <i>Xist</i><sup>Δhs</sup>, <i>mdx-Xist</i><sup>Δhs</sup> with <15% and 15–30% while the <i>mdx</i> and <i>mdx-Xist</i><sup>Δhs</sup> with >30% dystrophin performed significantly (<i>P</i><0.001) worse. Bad performance of <i>mdx-Xist</i><sup>Δhs</sup> with >30% was due to the bad performance of one individual mouse. E. Normalized fore limb grip strength was significantly (<i>P</i><0.001) higher in the <i>Xist</i><sup>Δhs</sup> mice compared to the other strains and all the <i>mdx-Xist</i><sup>Δhs</sup> mice were significantly (<i>P</i><0.001) stronger than the <i>mdx</i> mice. F. No difference in rotarod running was observed, except for the <i>mdx-Xist</i><sup>Δhs</sup> mice with 15–30% dystrophin, which performed significantly (<i>P</i><0.001) better than all other groups.</p>", "links"=>[], "tags"=>["ck", "levels"], "article_id"=>352908, "categories"=>["Physiology", "Genetics", "Neuroscience"], "users"=>["Maaike van Putten", "Margriet Hulsker", "Vishna Devi Nadarajah", "Sandra H. van Heiningen", "Ella van Huizen", "Maarten van Iterson", "Peter Admiraal", "Tobias Messemaker", "Johan T. den Dunnen", "Peter A. C. 't Hoen", "Annemieke Aartsma-Rus"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0031937.g002", "stats"=>{"downloads"=>0, "page_views"=>1, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Body_weight_CK_levels_and_functional_performance_of_the_mouse_models_/352908", "title"=>"Body weight, CK levels and functional performance of the mouse models.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-02-16 00:48:28"}
  • {"files"=>["https://ndownloader.figshare.com/files/348687", "https://ndownloader.figshare.com/files/348883"], "description"=>"<div><p>Duchenne muscular dystrophy (DMD) is a severe progressive muscular disorder caused by reading frame disrupting mutations in the <em>DMD</em> gene, preventing the synthesis of functional dystrophin. As dystrophin provides muscle fiber stability during contractions, dystrophin negative fibers are prone to exercise-induced damage. Upon exhaustion of the regenerative capacity, fibers will be replaced by fibrotic and fat tissue resulting in a progressive loss of function eventually leading to death in the early thirties. With several promising approaches for the treatment of DMD aiming at dystrophin restoration in clinical trials, there is an increasing need to determine more precisely which dystrophin levels are sufficient to restore muscle fiber integrity, protect against muscle damage and improve muscle function.</p> <p>To address this we generated a new mouse model (<em>mdx-Xist</em><sup>Δhs</sup>) with varying, low dystrophin levels (3–47%, mean 22.7%, stdev 12.1, <em>n</em> = 24) due to skewed X-inactivation. Longitudinal sections revealed that within individual fibers, some nuclei did and some did not express dystrophin, resulting in a random, mosaic pattern of dystrophin expression within fibers.</p> <p><em>Mdx-Xist</em><sup>Δhs</sup>, <em>mdx</em> and wild type females underwent a 12 week functional test regime consisting of different tests to assess muscle function at base line, or after chronic treadmill running exercise. Overall, <em>mdx-Xist</em><sup>Δhs</sup> mice with 3–14% dystrophin outperformed <em>mdx</em> mice in the functional tests. Improved histopathology was observed in mice with 15–29% dystrophin and these levels also resulted in normalized expression of pro-inflammatory biomarker genes, while for other parameters >30% of dystrophin was needed. Chronic exercise clearly worsened pathology, which needed dystrophin levels >20% for protection. Based on these findings, we conclude that while even dystrophin levels below 15% can improve pathology and performance, levels of >20% are needed to fully protect muscle fibers from exercise-induced damage.</p> </div>", "links"=>[], "tags"=>["effects", "levels", "dystrophin", "pathology"], "article_id"=>128938, "categories"=>["Physiology", "Genetics", "Neuroscience"], "users"=>["Maaike van Putten", "Margriet Hulsker", "Vishna Devi Nadarajah", "Sandra H. van Heiningen", "Ella van Huizen", "Maarten van Iterson", "Peter Admiraal", "Tobias Messemaker", "Johan T. den Dunnen", "Peter A. C. 't Hoen", "Annemieke Aartsma-Rus"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0031937.s001", "https://dx.doi.org/10.1371/journal.pone.0031937.s002"], "stats"=>{"downloads"=>2, "page_views"=>17, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/The_Effects_of_Low_Levels_of_Dystrophin_on_Mouse_Muscle_Function_and_Pathology/128938", "title"=>"The Effects of Low Levels of Dystrophin on Mouse Muscle Function and Pathology", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2012-02-16 02:28:58"}
  • {"files"=>["https://ndownloader.figshare.com/files/683029"], "description"=>"<p>A. Longest hanging time with the two limb hanging test was achieved by wild type and <i>mdx-Xist</i><sup>Δhs</sup> mice which both performed significantly (<i>P</i><0.001) better than <i>mdx</i> mice. B. Fore limb grip strength of <i>mdx-Xist</i><sup>Δhs</sup> mice was significantly (<i>P</i><0.001) better than that of <i>mdx</i> mice. C. Wild type mice outperformed <i>mdx</i> and <i>mdx-Xist</i><sup>Δhs</sup> mice on the rotarod, while no significant difference was observed between <i>mdx</i> and <i>mdx-Xist</i><sup>Δhs</sup> mice. Average dystrophin level of <i>mdx-Xist</i><sup>Δhs</sup> mice was 21% (2%–45% median 25.8).</p>", "links"=>[], "tags"=>["treadmill"], "article_id"=>353510, "categories"=>["Physiology", "Genetics", "Neuroscience"], "users"=>["Maaike van Putten", "Margriet Hulsker", "Vishna Devi Nadarajah", "Sandra H. van Heiningen", "Ella van Huizen", "Maarten van Iterson", "Peter Admiraal", "Tobias Messemaker", "Johan T. den Dunnen", "Peter A. C. 't Hoen", "Annemieke Aartsma-Rus"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0031937.g006", "stats"=>{"downloads"=>0, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Functional_performance_measured_directly_after_treadmill_exercise_/353510", "title"=>"Functional performance measured directly after treadmill exercise.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-02-16 00:58:30"}
  • {"files"=>["https://ndownloader.figshare.com/files/682603"], "description"=>"<p>A. Regenerating and hypertrophic fibers were mainly observed in the <i>mdx</i> mice. A dystrophin level depend trend towards wild type distribution was observed for <i>mdx-Xist</i><sup>Δhs</sup> mice where <15% dystrophin already resulted in improvement. B. Dystrophin levels between 15–30% and >30% resulted in a reduction of the percentage of centralized nuclei of 40% and 60% respectively. C. The quadriceps of all mice was significantly more severely affected compared to <i>Xist</i><sup>Δhs</sup> mice. D. The diaphragm was the most severely affected muscle with on average 20% fibrotic/necrotic tissue in <i>mdx</i> mice. All mice were significantly more severely affected compared to <i>Xist</i><sup>Δhs</sup> mice. <i>Mdx-Xist</i><sup>Δhs</sup> mice with >30% dystrophin had less fibrotic/necrotic tissue than <i>mdx</i> and <i>mdx-Xist</i><sup>Δhs</sup> mice with <15% dystrophin, but this difference was only significant between both <i>mdx-Xist</i><sup>Δhs</sup> groups. # indicates a significant difference of that bar with all the other groups. Single asterisks indicate a <i>P</i><0.05 and double asterisks indicate a <i>P</i><0.01.</p>", "links"=>[], "tags"=>["nucleation"], "article_id"=>353081, "categories"=>["Physiology", "Genetics", "Neuroscience"], "users"=>["Maaike van Putten", "Margriet Hulsker", "Vishna Devi Nadarajah", "Sandra H. van Heiningen", "Ella van Huizen", "Maarten van Iterson", "Peter Admiraal", "Tobias Messemaker", "Johan T. den Dunnen", "Peter A. C. 't Hoen", "Annemieke Aartsma-Rus"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0031937.g003", "stats"=>{"downloads"=>1, "page_views"=>20, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Muscle_fiber_size_degree_of_central_nucleation_and_percentage_of_fibrotic_necrotic_tissue_/353081", "title"=>"Muscle fiber size, degree of central nucleation and percentage of fibrotic/necrotic tissue.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-02-16 00:51:21"}
  • {"files"=>["https://ndownloader.figshare.com/files/682914"], "description"=>"<p>A. CK levels assessed before and directly after treadmill running. CK levels collected before exercise were significantly (<i>P</i><0.01) lower than those collected directly after exercise in <i>mdx-Xist</i><sup>Δhs</sup> and <i>mdx</i> mice. This exercise induced increase was absent in wild type mice. B. CK levels determined before exercise were significantly (<i>P</i><0.01) elevated in <i>mdx</i> and <i>mdx-Xist</i><sup>Δhs</sup> mice compared to wild type, but this was less pronounced for the <i>mdx-Xist</i><sup>Δhs</sup> mice as <i>mdx</i> mice had significantly (<i>P</i><0.05) higher CK levels. C. Plasma collected directly after exercise contained extremely high CK levels, in both <i>mdx</i> and <i>mdx-Xist</i><sup>Δhs</sup> mice but not in wild type mice. D. Serum levels of MMP-9 were elevated in <i>mdx</i> mice compared to <i>Xist</i><sup>Δhs</sup> mice at both 8 and 14 weeks of age, while levels were normalized in <i>mdx-Xist</i><sup>Δhs</sup> mice. E. TIMP-1 levels were elevated in serum of both <i>mdx</i> and <i>mdx-Xist</i><sup>Δhs</sup> mice. In wild type mice we found an age related increase of the serum TIMP-1 level. Interestingly, at the age of 8 weeks, levels of <i>mdx-Xist</i><sup>Δhs</sup> mice were significantly lower than those of <i>mdx</i> mice. F. <i>Mdx</i> mice had significantly elevated OPN levels compared to both wild type and <i>mdx-Xist</i><sup>Δhs</sup> at 8 weeks of age. Single asterisks indicate a <i>P</i><0.05, average dystrophin level of <i>mdx-Xist</i><sup>Δhs</sup> mice was 21% (2%–45% median 25.8).</p>", "links"=>[], "tags"=>["plasma", "biomarkers", "assessed", "treadmill"], "article_id"=>353386, "categories"=>["Physiology", "Genetics", "Neuroscience"], "users"=>["Maaike van Putten", "Margriet Hulsker", "Vishna Devi Nadarajah", "Sandra H. van Heiningen", "Ella van Huizen", "Maarten van Iterson", "Peter Admiraal", "Tobias Messemaker", "Johan T. den Dunnen", "Peter A. C. 't Hoen", "Annemieke Aartsma-Rus"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0031937.g005", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Serum_and_plasma_biomarkers_assessed_before_and_directly_after_treadmill_running_/353386", "title"=>"Serum and plasma biomarkers assessed before and directly after treadmill running.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-02-16 00:56:26"}
  • {"files"=>["https://ndownloader.figshare.com/files/682251"], "description"=>"<p>A. To breed mice with low dystrophin levels, female <i>Xist</i><sup>Δhs</sup> mice, carrying a mutation in the <i>Xist</i> promoter which coordinates X-inactivation, were crossed with dystrophin negative <i>mdx</i> males. During embryogenesis, the maternal X-chromosome encoding a functional dystrophin gene will be preferentially (60–90%) inactivated as a result of the mutated <i>Xist</i> promoter. The <i>Xist</i><sup>Δhs</sup> mice were a kind gift from N. Brockdorff (MRC Clinical Sciences Center, London, UK, current affiliation Department of Biochemistry, University of Oxford, UK). B. Picture of a representative Western blot. The percentage of dystrophin was determined for the quadriceps of all <i>mdx-Xist</i><sup>Δhs</sup> mice by Western blot (2–9 technical replicates per mouse). The percentage of individual mice was determined using a concentration curve made from wild type samples. Myosin was used as a loading control. C. Skewed X-inactivation resulted in dystrophin levels of 3–47% (mean 22.7, stdev 12.1, <i>n</i> = 24) (as determined by Western blot) in the female <i>mdx-Xist</i><sup>Δhs</sup> offspring. Each bar represents the dystrophin level of an individual mouse. The dystrophin levels of the individual mice belonging to the three dystrophin groups can be appreciated from this graph. D. Dystrophin levels determined by Western blot and manual counting of dystrophin positive fibers demonstrate a strong correlation (R = 0.97). E. Longitudinal sections of a quadriceps stained with dystrophin (green) and spectrin (red). From the pictures it can be appreciated that dystrophin expression is not homogeneously expressed across the fiber but rather confined to certain nuclear domains.</p>", "links"=>[], "tags"=>["genetics and genomics", "physiology", "neurological disorders"], "article_id"=>352728, "categories"=>["Physiology", "Genetics", "Neuroscience"], "users"=>["Maaike van Putten", "Margriet Hulsker", "Vishna Devi Nadarajah", "Sandra H. van Heiningen", "Ella van Huizen", "Maarten van Iterson", "Peter Admiraal", "Tobias Messemaker", "Johan T. den Dunnen", "Peter A. C. 't Hoen", "Annemieke Aartsma-Rus"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0031937.g001", "stats"=>{"downloads"=>1, "page_views"=>11, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Mdx_Xist_916_hs_mice_/352728", "title"=>"<i>Mdx-Xist</i><sup>Δhs</sup> mice.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-02-16 00:45:28"}
  • {"files"=>["https://ndownloader.figshare.com/files/683163"], "description"=>"<p>A. Wild type mice were less severely affected than <i>mdx</i> and <i>mdx-Xist</i><sup>Δhs</sup> mice. Due to high variation between individual <i>mdx</i> mice, the difference between <i>mdx</i> and wild type mice was not significant. <i>Mdx-Xist</i><sup>Δhs</sup> mice had slightly less fibrotic tissue than <i>mdx</i> mice. B. No difference in expression of genes involved in disease pathology was found between <i>mdx</i> and <i>mdx-Xist</i><sup>Δhs</sup> mice. Both mouse strains did differ significantly from wild type mice, of which the expression levels were low. Single and double asterisks indicate a <i>P</i><0.05 and <i>P</i><0.01, respectively. # Indicates a significant difference from all other groups, average dystrophin levels of <i>mdx-Xist</i><sup>Δhs</sup> mice was 21% (2%–45% median 25.8).</p>", "links"=>[], "tags"=>["induced", "histopathology", "biomarker"], "article_id"=>353638, "categories"=>["Physiology", "Genetics", "Neuroscience"], "users"=>["Maaike van Putten", "Margriet Hulsker", "Vishna Devi Nadarajah", "Sandra H. van Heiningen", "Ella van Huizen", "Maarten van Iterson", "Peter Admiraal", "Tobias Messemaker", "Johan T. den Dunnen", "Peter A. C. 't Hoen", "Annemieke Aartsma-Rus"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0031937.g007", "stats"=>{"downloads"=>0, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Exercise_induced_histopathology_and_biomarker_gene_expression_/353638", "title"=>"Exercise induced histopathology and biomarker gene expression.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-02-16 01:00:38"}
  • {"files"=>["https://ndownloader.figshare.com/files/682767"], "description"=>"<p>A and B. For most biomarkers a clear dystrophin level dependent restoration of gene expression levels was observed in the <i>mdx-Xist</i><sup>Δhs</sup> mice, where intermediate dystrophin levels resulted in low expression of genes involved in disease pathology. For some genes, dystrophin levels <15% were enough to reduce gene expression while for other genes >30% was necessary. C. In the heart, even dystrophin levels of <15% decreased expression of fibrotic biomarkers like <i>Timp-1</i>. Since the mice were young, no difference in expression levels in heart function was observed, except for <i>Nppa</i>. Double asterisks indicate a <i>P</i><0.01.</p>", "links"=>[], "tags"=>["genes"], "article_id"=>353247, "categories"=>["Physiology", "Genetics", "Neuroscience"], "users"=>["Maaike van Putten", "Margriet Hulsker", "Vishna Devi Nadarajah", "Sandra H. van Heiningen", "Ella van Huizen", "Maarten van Iterson", "Peter Admiraal", "Tobias Messemaker", "Johan T. den Dunnen", "Peter A. C. 't Hoen", "Annemieke Aartsma-Rus"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0031937.g004", "stats"=>{"downloads"=>1, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Expression_of_several_genes_involved_in_disease_pathology_/353247", "title"=>"Expression of several genes involved in disease pathology.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-02-16 00:54:07"}

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