Noninvasive in vivo assessment of muscle impairment in the mdx mouse model--a comparison of two common wire hanging methods with two different results.
Duchenne muscular dystrophy (DMD) is an X-chromosome-linked disorder that arises from a mutation in the gene for the cytoskeletal protein dystrophin, normally expressed in the myofibres. The most widely applied animal model in DMD basic research is the C57BL/10ScSn-mdx/J mouse, commonly referred to as the "mdx mouse". The potential benefit of novel interventions in this in vivo model is often assessed by functioning tests, as the improvement of muscle impairment is the final goal of all approaches to treat DMD. In this study we compared two (TWHT) and four limb wire hanging tests (FWHT) for utility in evaluating muscle impairment in the mdx-mouse relative to its C57BL/10 wild-type counterpart. Our objective was to determine an optimal approach to perform wire hanging measurements in this model system such that latency to fall is indicative of the dystrophic phenotype that provides a quantitative measure of its presentation, and can be used to assess functional improvements that result from therapeutic intervention. Surprisingly the results of the latency times in the TWHT did not allow discrimination between the mdx population and their healthy counterparts, whereas hanging times in the FWHT enabled ready discrimination between the muscle function of mutant and wild-type animals. Furthermore, we analyzed confounding factors that explain the strengths and weaknesses of each wire hanging test configuration. The results of this study are of relevance for investigators who rely on pre clinical function tests to assess potential therapies in DMD.
Center of Musculoskeletal Disorders, University Hospital of Regensburg, Franz-Josef-Strauss-Allee 11, 93053 Regensburg, Germany. Silvan.Klein@klinik.uni-regensburg.de
Silvan M
SM
Klein
Jody
J
Vykoukal
Philipp
P
Lechler
Katharina
K
Zeitler
Sebastian
S
Gehmert
Stephan
S
Schreml
Eckhard
E
Alt
Ulrich
U
Bogdahn
Lukas
L
Prantl
D000818:Animals; D004195:Disease Models, Animal; D005121:Extremities / Q000503:physiopathology*; D005260:Female; D006799:Housing, Animal / Q000592:standards; D051379:Mice; D008810:Mice, Inbred C57BL; D018101:Mice, Inbred mdx; D018908:Muscle Weakness / Q000175:diagnosis* / Q000235:genetics / Q000503:physiopathology; D018482:Muscle, Skeletal / Q000378:metabolism / Q000503:physiopathology*