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

Overview

Journal Thyroid

Date 2016 Dec 15

PMID 27967605

Citations 6

Authors

Daniele L Ignacio

Diego H S Silvestre

Elena Anne-Palmer

Barbara M L C Bocco

Tatiana L Fonseca

Miriam O Ribeiro

Balazs Gereben

Antonio C Bianco

Joao P Werneck-de-Castro

Affiliations

Soon will be listed here.

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.

Citing Articles

Selenium Status and Its Antioxidant Role in Metabolic Diseases.

Huang J, Xie L, Song A, Zhang C Oxid Med Cell Longev. 2022; 2022:7009863.

PMID: 35847596 PMC: 9279078. DOI: 10.1155/2022/7009863.

Serine Administration Improves Selenium Status, Oxidative Stress, and Mitochondrial Function in Longissimus Dorsi Muscle of Piglets with Intrauterine Growth Retardation.

He Y, Liu Y, Guan P, He L, Zhou X Biol Trace Elem Res. 2022; 201(4):1740-1747.

PMID: 35661959 DOI: 10.1007/s12011-022-03304-5.

Deiodinases and their intricate role in thyroid hormone homeostasis.

Luongo C, Dentice M, Salvatore D Nat Rev Endocrinol. 2019; 15(8):479-488.

PMID: 31160732 DOI: 10.1038/s41574-019-0218-2.

Paradigms of Dynamic Control of Thyroid Hormone Signaling.

Bianco A, Dumitrescu A, Gereben B, Ribeiro M, Fonseca T, Fernandes G Endocr Rev. 2019; 40(4):1000-1047.

PMID: 31033998 PMC: 6596318. DOI: 10.1210/er.2018-00275.

A Global Loss of Dio2 Leads to Unexpected Changes in Function and Fiber Types of Slow Skeletal Muscle in Male Mice.

Carmody C, Ogawa-Wong A, Martin C, Luongo C, Zuidwijk M, Sager B Endocrinology. 2019; 160(5):1205-1222.

PMID: 30951174 PMC: 6482039. DOI: 10.1210/en.2019-00088.

References

Sagar G, Gereben B, Callebaut I, Mornon J, Zeold A, Curcio-Morelli C . The thyroid hormone-inactivating deiodinase functions as a homodimer. Mol Endocrinol. 2008; 22(6):1382-93. PMC: 2422829. DOI: 10.1210/me.2007-0490. View

Erkintalo M, Bendahan D, Mattei J, Fabreguettes C, Vague P, Cozzone P . Reduced metabolic efficiency of skeletal muscle energetics in hyperthyroid patients evidenced quantitatively by in vivo phosphorus-31 magnetic resonance spectroscopy. Metabolism. 1998; 47(7):769-76. DOI: 10.1016/s0026-0495(98)90110-x. View

Schiaffino S, Reggiani C . Fiber types in mammalian skeletal muscles. Physiol Rev. 2011; 91(4):1447-531. DOI: 10.1152/physrev.00031.2010. View

Gharaibeh B, Lu A, Tebbets J, Zheng B, Feduska J, Crisan M . Isolation of a slowly adhering cell fraction containing stem cells from murine skeletal muscle by the preplate technique. Nat Protoc. 2008; 3(9):1501-9. DOI: 10.1038/nprot.2008.142. View

Kassar-Duchossoy L, Gayraud-Morel B, Gomes D, Rocancourt D, Buckingham M, Shinin V . Mrf4 determines skeletal muscle identity in Myf5:Myod double-mutant mice. Nature. 2004; 431(7007):466-71. DOI: 10.1038/nature02876. View

Moncaut N, Rigby P, Carvajal J . Dial M(RF) for myogenesis. FEBS J. 2013; 280(17):3980-90. DOI: 10.1111/febs.12379. View

Comai G, Sambasivan R, Gopalakrishnan S, Tajbakhsh S . Variations in the efficiency of lineage marking and ablation confound distinctions between myogenic cell populations. Dev Cell. 2014; 31(5):654-67. DOI: 10.1016/j.devcel.2014.11.005. View

Rudnicki M, Braun T, Hinuma S, Jaenisch R . Inactivation of MyoD in mice leads to up-regulation of the myogenic HLH gene Myf-5 and results in apparently normal muscle development. Cell. 1992; 71(3):383-90. DOI: 10.1016/0092-8674(92)90508-a. View

Chen J, Mortimer J, Marley J, Goldhamer D . MyoD-cre transgenic mice: a model for conditional mutagenesis and lineage tracing of skeletal muscle. Genesis. 2005; 41(3):116-21. DOI: 10.1002/gene.20104. View

10.

Salvatore D, Simonides W, Dentice M, Zavacki A, Larsen P . Thyroid hormones and skeletal muscle--new insights and potential implications. Nat Rev Endocrinol. 2013; 10(4):206-14. PMC: 4037849. DOI: 10.1038/nrendo.2013.238. View

11.

Werneck-de-Castro J, Fonseca T, Ignacio D, Fernandes G, Andrade-Feraud C, Lartey L . Thyroid Hormone Signaling in Male Mouse Skeletal Muscle Is Largely Independent of D2 in Myocytes. Endocrinology. 2015; 156(10):3842-52. PMC: 4588812. DOI: 10.1210/en.2015-1246. View

12.

Arrojo E Drigo R, Fonseca T, Werneck-de-Castro J, Bianco A . Role of the type 2 iodothyronine deiodinase (D2) in the control of thyroid hormone signaling. Biochim Biophys Acta. 2012; 1830(7):3956-64. PMC: 4979226. DOI: 10.1016/j.bbagen.2012.08.019. View

13.

Marsili A, Aguayo-Mazzucato C, Chen T, Kumar A, Chung M, Lunsford E . Mice with a targeted deletion of the type 2 deiodinase are insulin resistant and susceptible to diet induced obesity. PLoS One. 2011; 6(6):e20832. PMC: 3116839. DOI: 10.1371/journal.pone.0020832. View

14.

Monzani F, Caraccio N, Siciliano G, Manca L, Murri L, Ferrannini E . Clinical and biochemical features of muscle dysfunction in subclinical hypothyroidism. J Clin Endocrinol Metab. 1997; 82(10):3315-8. DOI: 10.1210/jcem.82.10.4296. View

15.

Visser W, Heemstra K, Swagemakers S, Ozgur Z, Corssmit E, Burggraaf J . Physiological thyroid hormone levels regulate numerous skeletal muscle transcripts. J Clin Endocrinol Metab. 2009; 94(9):3487-96. DOI: 10.1210/jc.2009-0782. View

16.

Khaleeli A, GRIFFITH D, EDWARDS R . The clinical presentation of hypothyroid myopathy and its relationship to abnormalities in structure and function of skeletal muscle. Clin Endocrinol (Oxf). 1983; 19(3):365-76. DOI: 10.1111/j.1365-2265.1983.tb00010.x. View

17.

Dentice M, Marsili A, Ambrosio R, Guardiola O, Sibilio A, Paik J . The FoxO3/type 2 deiodinase pathway is required for normal mouse myogenesis and muscle regeneration. J Clin Invest. 2010; 120(11):4021-30. PMC: 2964991. DOI: 10.1172/JCI43670. View

18.

Schneider M, Fiering S, Pallud S, Parlow A, St Germain D, Galton V . Targeted disruption of the type 2 selenodeiodinase gene (DIO2) results in a phenotype of pituitary resistance to T4. Mol Endocrinol. 2001; 15(12):2137-48. DOI: 10.1210/mend.15.12.0740. View

19.

Milanesi A, Lee J, Kim N, Liu Y, Yang A, Sedrakyan S . Thyroid Hormone Receptor α Plays an Essential Role in Male Skeletal Muscle Myoblast Proliferation, Differentiation, and Response to Injury. Endocrinology. 2015; 157(1):4-15. PMC: 4701883. DOI: 10.1210/en.2015-1443. View

20.

Seale P, Bjork B, Yang W, Kajimura S, Chin S, Kuang S . PRDM16 controls a brown fat/skeletal muscle switch. Nature. 2008; 454(7207):961-7. PMC: 2583329. DOI: 10.1038/nature07182. View