PMID:21209367

Citation	Lovering, RM, O'Neill, A, Muriel, JM, Prosser, BL, Strong, J and Bloch, RJ (2011) Physiology, structure, and susceptibility to injury of skeletal muscle in mice lacking keratin 19-based and desmin-based intermediate filaments. Am. J. Physiol., Cell Physiol. 300:C803-13
Abstract	Intermediate filaments, composed of desmin and of keratins, play important roles in linking contractile elements to each other and to the sarcolemma in striated muscle. Our previous results show that the tibialis anterior (TA) muscles of mice lacking keratin 19 (K19) lose costameres, accumulate mitochondria under the sarcolemma, and generate lower specific tension than controls. Here we compare the physiology and morphology of TA muscles of mice lacking K19 with muscles lacking desmin or both proteins [double knockout (DKO)]. K19-/- mice and DKO mice showed a threefold increase in the levels of creatine kinase (CK) in the serum. The absence of desmin caused a larger change in specific tension (-40%) than the absence of K19 (-19%) and played the predominant role in contractile function (-40%) and decreased tolerance to exercise in the DKO muscle. By contrast, the absence of both proteins was required to obtain a significantly greater loss of contractile torque after injury (-48%) compared with wild type (-39%), as well as near-complete disruption of costameres. The DKO muscle also showed a significantly greater misalignment of myofibrils than either mutant alone. In contrast, large subsarcolemmal gaps and extensive accumulation of mitochondria were only seen in K19-null TA muscles, and the absence of both K19 and desmin yielded milder phenotypes. Our results suggest that keratin filaments containing K19- and desmin-based intermediate filaments can play independent, complementary, or antagonistic roles in the physiology and morphology of fast-twitch skeletal muscle.
Links	PubMed PMC3074621 Online version:10.1152/ajpcell.00394.2010
Keywords	Animals; Desmin/genetics; Desmin/metabolism; Female; Intermediate Filament Proteins/genetics; Intermediate Filament Proteins/metabolism; Intermediate Filaments/metabolism; Keratin-19/genetics; Keratin-19/metabolism; Male; Mice; Mice, Knockout; Motor Activity/physiology; Muscle Contraction/physiology; Muscle Fibers, Fast-Twitch/metabolism; Muscle Fibers, Fast-Twitch/ultrastructure; Muscle, Skeletal/injuries; Muscle, Skeletal/physiology; Muscle, Skeletal/ultrastructure; Sarcolemma/metabolism; Sarcolemma/ultrastructure
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
MOUSE:DESM		GO:0014873: response to muscle activity involved in regulation of muscle adaptation	ECO:0000315:		P		Figure 6, Figure 7	complete
MOUSE:DESM		GO:0048312: intracellular distribution of mitochondria	ECO:0000315:		P		Figure 2 G	complete
MOUSE:K1C19		GO:0048312: intracellular distribution of mitochondria	ECO:0000315:		P		Figure 2 G	complete

References

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