A simple protocol for assessing inter-trial and inter-examiner reliability for two noninvasive measures of limb muscle strength.

Noninvasive measures of limb muscle strength are quite useful in preclinical translational studies that use mouse models of muscle disease, peripheral nerve disease, and movement disorders. The present study uses a simple protocol for assessing both inter-trial and inter-examiner reliability for two noninvasive methods of assessing limb strength in dystrophic (mdx) and wild type mice. One method, termed the whole body tension (WBT) method or escape test, measures the total phasic pulling tension exerted by the fore- and hindlimbs while a mouse attempts to escape into a darkened tube. Another procedure, termed the four limb wire grid holding test, measures the minimal amount of sustained tension (physical impulse) exerted by the fore- and hindlimbs while the mouse hangs suspended in an upside-down position. A comparison of the two methods revealed significant inter-trial and inter-examiner correlations in each procedure, although the WBT procedure consistently produced higher correlations than the four limb wire grid holding test. Inter-trial reliability for each test was higher than inter-examiner reliability, indicating that each longitudinal series of tests is best performed by a single investigator. The holding test also did not consistently detect differences between wild type and mdx populations at ages greater than 4 months. These results demonstrate the utility of a simple protocol for assessing the reliability of noninvasive tests that measure limb strength, and should be useful in comparing different functional measures in a broad range of translational studies.

Treatment with inhibitors of the NF-kappaB pathway improves whole body tension development in the mdx mouse.

The whole body tension (WBT) method was used to evaluate the hypothesis that long term treatment with NF-kappaB inhibitors improves the total forward pulling tension exerted by the limb musculature of the mdx mouse. Mdx mice exhibited significantly reduced WBT values and more profound weakening during the course of generating multiple forward pulling movements than age-matched nondystrophic mice. Long term treatment with the NF-kappaB inhibitor pyrrolidine dithiocarbamate (PDTC) did not significantly reduce nuclear p65 activation in the costal diaphragm, but increased WBT by 12% in mature (12 month) mice. Daily treatment (30 days) of 1 month old mdx mice with the inhibitor ursodeoxycholic acid (UDCA) reduced costal diaphragm nuclear p65 activation by 40% and increased WBT by 21%. These results indicate that treatment with NF-kappaB inhibitors improves WBT in the mdx mouse and further establishes the utility of the WBT procedure in assessing therapeutic efficacy.