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Developmental Genetics Programme, The Babraham Institute, Cambridge CB2 4AT, UK; and
* Department of Physiology, University of Cambridge, Cambridge CB2 3EG, UK
1Correspondence: The Babraham Institute, Bldg. 540, Babraham Hall, Cambridge CB2 4AT, UK. E-mail: joy.dauncey{at}bbsrc.ac.uk
Nuclear thyroid hormone (TH) receptors (TR) play a critical role in
mediating the diverse actions of TH in development, differentiation,
and metabolism of most tissues, but the role of TR isoforms in muscle
development and function is unclear. Therefore, we have undertaken a
comprehensive expression analysis of TR
1, TRß 1, TRß 2 (TH
binding), and TR 2 (non-TH binding) in functionally distinct porcine
muscles during prenatal and postnatal development. Use of a novel and
highly sensitive RNase protection assay revealed striking
muscle-specific developmental profiles of all four TR isoform mRNAs in
cardiac, longissimus, soleus, rhomboideus, and diaphragm. Distribution
of TR isoforms varied markedly between muscles; TR expression was
considerably greater than TRß and there were significant differences
in the ratios TR 1:TR 2, and TRß 1:TRß 2. Together with
immunohistochemistry of myosin heavy chain isoforms and data on
myogenesis and maturation of the TH axis, these findings provide new
evidence that highlights central roles for 1) TR
isoforms in fetal myogenesis, 2) the ratio TR 1:TR
2 in determining cardiac and skeletal muscle phenotype and function;
3) TRß in maintaining a basal level of cellular
response to TH throughout development and a specific maturational
function around birth. These findings suggest that events disrupting
normal developmental profiles of TR isoforms may impair optimal
function of cardiac and skeletal muscles.—White, P., Burton, K. A., Fowden, A. L., Dauncey, M. J. Developmental expression
analysis of thyroid hormone receptor isoforms reveals new insights into
their essential functions in cardiac and skeletal muscles.
Key Words: cardiac and skeletal muscle • myosin • prenatal and postnatal development • TR
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