title: Early Developmental Disruption of Type 2 Deiodinase Pathway in Mouse Skeletal Muscle Does Not Impair Muscle Function.
abstract: Myogenesis is positively regulated by thyroid hormone (triiodothyronine [T3]), which is amplified by the type 2 deiodinase (D2) activation of thyroxine to T3. Global inactivation of the Dio2 gene impairs skeletal muscle (SKM) differentiation and regeneration in response to muscle injury. Given that newborn and adult mice with late developmental SKM Dio2 disruption do not develop a significant phenotype, it was hypothesized that D2 plays an early role in this process.
  
  
  
  This was tested in mice with SKM disruption of Dio2 driven by two early developmental promoters: MYF5 and MYOD.
  
  
  
  MYF5 myoblasts in culture differentiate normally into myotubes, despite loss of almost all D2 activity. Dio2 mRNA levels in developing SKM obtained from MYF5-D2KO embryos (E18.5) were about 54% of control littermates, but the expression of the T3-responsive genes Myh1 and 7 and Atp2a1 and 2 were not affected. In MYF5-D2KO and MYOD-D2KO neonatal hind-limb muscle, the expression of Myh1 and 7 and Atp2a2 remained unaffected, despite 60-70% loss in D2 activity and/or mRNA. Only in MYOD-D2KO neonatal muscle was there a 40% reduction in Atp2a1 mRNA. Postnatal growth of both mouse models and SKM function as assessed by exercise capacity and measurement of muscle strength were normal. Furthermore, an analysis of the adult soleus revealed no changes in the expression of T3-responsive genes, except for an about 18% increase in MYOD-D2KO SOL Myh7 mRNA.
  
  
  
  Two mouse models of early developmental disruption of Dio2 in myocyte precursor exhibit no significant SKM phenotype.
authors.affiliation: 1 Division of Endocrinology and Metabolism, Rush University Medical Center , Chicago, Illinois.|2 Biophysics Institute and School of Physical Education and Sports, Federal University of Rio de Janeiro , Rio de Janeiro, Brazil .
authors.forename: Daniele L
authors.initials: DL
authors.lastname: Ignacio
authors.affiliation: 1 Division of Endocrinology and Metabolism, Rush University Medical Center , Chicago, Illinois.|2 Biophysics Institute and School of Physical Education and Sports, Federal University of Rio de Janeiro , Rio de Janeiro, Brazil .|3 Nutrition Institute Josué de Castro, Federal University of Rio de Janeiro , Rio de Janeiro, Brazil .
authors.forename: Diego H S
authors.initials: DH
authors.lastname: Silvestre
authors.affiliation: 1 Division of Endocrinology and Metabolism, Rush University Medical Center , Chicago, Illinois.
authors.forename: Elena
authors.initials: E
authors.lastname: Anne-Palmer
authors.affiliation: 1 Division of Endocrinology and Metabolism, Rush University Medical Center , Chicago, Illinois.|4 Department of Translational Medicine, Federal University of São Paulo , São Paulo, Brazil .
authors.forename: Barbara M L C
authors.initials: BM
authors.lastname: Bocco
authors.affiliation: 1 Division of Endocrinology and Metabolism, Rush University Medical Center , Chicago, Illinois.
authors.forename: Tatiana L
authors.initials: TL
authors.lastname: Fonseca
authors.affiliation: 5 Developmental Disorders Program, Center for Biological and Health Sciences, Mackenzie Presbyterian University , São Paulo, Brazil .
authors.forename: Miriam O
authors.initials: MO
authors.lastname: Ribeiro
authors.affiliation: 6 Department of Endocrine Neurobiology, Institute of Experimental Medicine , Hungarian Academy of Sciences, Budapest, Hungary .
authors.forename: Balázs
authors.initials: B
authors.lastname: Gereben
authors.affiliation: 1 Division of Endocrinology and Metabolism, Rush University Medical Center , Chicago, Illinois.
authors.forename: Antonio C
authors.initials: AC
authors.lastname: Bianco
authors.affiliation: 1 Division of Endocrinology and Metabolism, Rush University Medical Center , Chicago, Illinois.|2 Biophysics Institute and School of Physical Education and Sports, Federal University of Rio de Janeiro , Rio de Janeiro, Brazil .|3 Nutrition Institute Josué de Castro, Federal University of Rio de Janeiro , Rio de Janeiro, Brazil .
authors.forename: Joao P
authors.initials: JP
authors.lastname: Werneck-de-Castro
mesh_terms: D000818:Animals; D018507:Gene Expression Regulation, Developmental; D007453:Iodide Peroxidase / Q000235:genetics*; D051379:Mice; D018345:Mice, Knockout; D024510:Muscle Development / Q000235:genetics*; D018482:Muscle, Skeletal / Q000254:growth & development* / Q000378:metabolism; D017570:MyoD Protein / Q000235:genetics; D032446:Myoblasts / Q000378:metabolism*; D051787:Myogenic Regulatory Factor 5 / Q000235:genetics; D018995:Myosin Heavy Chains / Q000235:genetics; D010641:Phenotype; D012333:RNA, Messenger / Q000378:metabolism*; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000235:genetics; D015398:Signal Transduction; D014284:Triiodothyronine / Q000378:metabolism*; D000097564:Iodothyronine Deiodinase Type II
chemical_list: D007453:Iodide Peroxidase; D017570:MyoD Protein; D051787:Myogenic Regulatory Factor 5; D018995:Myosin Heavy Chains; D012333:RNA, Messenger; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D014284:Triiodothyronine; D000097564:Iodothyronine Deiodinase Type II; C497418:Myf5 protein, mouse; C551613:Myh7 protein, mouse; C057363:MyoD1 myogenic differentiation protein; C506947:Atp2a2 protein, mouse
keywords: deiodinases; myogenesis; skeletal muscle function; thyroid hormone signaling