Soluble activin receptor type IIB increases forward pulling tension in the mdx mouse.

INTRODUCTION: In this study we investigated the action of RAP-031, a soluble activin receptor type IIB (ActRIIB) comprised of a form of the ActRIIB extracellular domain linked to a murine Fc, and the NF-κB inhibitor, ursodeoxycholic acid (UDCA), on the whole body strength of mdx mice. METHODS: The whole body tension (WBT) method of assessing the forward pulling tension (FPT) exerted by dystrophic (mdx) mice was used. RESULTS: RAP-031 produced a 41% increase in body mass and a 42.5% increase in FPT without altering the FPT normalized for body mass (WBT). Coadministration of RAP-031 with UDCA produced increases in FPT that were associated with an increase in WBT. CONCLUSIONS: Myostatin inhibition increases muscle mass without altering the fundamental weakness characteristic of dystrophic muscle. Cotreatment with an NF-κB inhibitor potentiates the effects of myostatin inhibition in improving FPT in mdx mice.

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.