Early Developmental Disruption of Type 2 Deiodinase Pathway in Mouse Skeletal Muscle Does Not Impair Muscle Function

Daniele L. Ignacio, Diego H.S. Silvestre, Elena Anne-Palmer, Barbara M.L.C. Bocco, Tatiana L. Fonseca, Miriam O. Ribeiro, Balázs Gereben, Antonio Bianco, Joao P. Werneck-De-Castro

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

Background: 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. Methods: This was tested in mice with SKM disruption of Dio2 driven by two early developmental promoters: MYF5 and MYOD. Results: 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. Conclusion: Two mouse models of early developmental disruption of Dio2 in myocyte precursor exhibit no significant SKM phenotype.

Original languageEnglish (US)
Pages (from-to)577-586
Number of pages10
JournalThyroid
Volume27
Issue number4
DOIs
StatePublished - Apr 2017
Externally publishedYes

Keywords

  • deiodinases
  • myogenesis
  • skeletal muscle function
  • thyroid hormone signaling

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

Fingerprint

Dive into the research topics of 'Early Developmental Disruption of Type 2 Deiodinase Pathway in Mouse Skeletal Muscle Does Not Impair Muscle Function'. Together they form a unique fingerprint.

Cite this