Skeletal muscle of mice with a mutation in slow alpha-tropomyosin is weaker at lower lengths.
Skeletal muscle function was measured in anaesthetised transgenic mice having a mutation in the TPM3 gene (slow alpha-tropomyosin), a similar mutation as found in some patients with nemaline myopathy, and was compared with control muscles. Measurements of isometric and dynamic muscle performance were done with electrical nerve stimulation at physiological temperatures. No muscle weakness was found in the transgenic muscles when performance was measured at muscle optimum length. This was true not only with full activation but also at lower activation levels, indicating that calcium sensitivity was not affected at this length. Also, fatigability was not affected in these conditions. However, isometric force of the muscles with the mutation in TPM3 was lower at lengths below optimum, with more impairment at decreasing length. As the muscles are active over a large range of different muscle lengths during daily activities, this finding may explain, at least in part, the muscle weakness experienced by patients with nemaline myopathy.
de Haan
A
A
Institute for Fundamental and Clinical Human Movement Sciences, Faculty of Human Movement Sciences, Vrije University, Van der Boechorststraat 9, 1081 BT, Amsterdam, The Netherlands. a.dehaan@fbw.vu.nl
van der Vliet
M R
MR
Gommans
I M P
IM
Hardeman
E C
EC
van Engelen
B G M
BG
D000818:Animals; D004558:Electric Stimulation; D005260:Female; D066298:In Vitro Techniques; D007537:Isometric Contraction / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D018763:Muscle Fatigue / Q000235:genetics / Q000502:physiology; D018908:Muscle Weakness / Q000235:genetics* / Q000503:physiopathology; D018482:Muscle, Skeletal / Q000503:physiopathology*; D009154:Mutation; D014335:Tropomyosin / Q000235:genetics*
C411923:Tpm3 protein, mouse; D014335:Tropomyosin