Abstract
The loss of the slow skeletal muscle isoform of troponin T (ssTnT) encoded by TNNT1 causes lethal myopathies with symptoms including abnormal neuromuscular reflexes. It has been a challenging question that how the loss of one isoform of TnT results in extremely severe phenotypes while the fast isoform of TnT is present in the patient muscles. We investigated ssTnT knockout (KO) mice for the role of ssTnT in muscle spindles that are a mechanosensors critical to normal neuromuscular function. Immunohistological and spindle protein content studies indicated that unlike extrafusal muscle fibers, adult ssTnT-KO mouse spindle intrafusal fibers express high levels of cardiac TnT, which is significantly increased in intrafusal fibers of ssTnT-KO mice. Impaired motor coordination was observed in ssTnT-KO mice with slower walking during a balance beam performance test as compared with age/sex-matched wildtype (WT) control (p<0.05). An interesting observation from the balance beam performance test is that subcutaneous injection of succinylcholine (SCh), a muscle relaxant believed to alter spindle activities, significantly increased the time for WT mice to walk across the balance beam (p<0.01) whereas SCh treatment produced a trend for decreased time across the beam in ssTnT-KO mice (p=0.10). Taken together, our data suggest that the loss of ssTnT in the KO mice impairs spindle intrafusal fiber contractility, identifying a novel therapeutic target. The attenuated effect of SCh treatment on motor coordination in the ssTnT-KO mice may be due to the potentially adaptive increased expression of cardiac TnT in spindle intrafusal fibers. Further testing is currently underway to assessing the hypothesized adaptation of spindle intrafusal fiber TnT isoform expression and function in ssTnT-KO mice during postnatal development.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.