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.
