Consequence of parvalbumin deficiency in the mdx mouse: histological, biochemical and mechanical phenotype of a new double mutant.
We tested the hypothesis whether the mild dystrophy in mdx mice could result from the contribution of the cytosolic calcium buffer parvalbumin in maintaining a normal cytosolic [Ca2+]i, in spite of an increased passive Ca2+ influx. By crossing mdx mice with parvalbumin-deficient mice, double mutant mice, lacking both dystrophin and parvalbumin, were obtained. Though resting cytosolic [Ca2+]i and total calcium content were similar to that of mdx muscles, this new animal model presented a slightly more severe phenotype than the mdx mouse. Muscle pseudo-hypertrophy, the density of myotubes and of centronucleated fibres as well as the loss of IIB fibres were all increased in parvalbumin-deficient mdx mice. Many of these deficits were overcome in late adulthood, albeit fibrosis was clearly more pronounced than in mdx muscles. At 90 days, parvalbumin-deficient mdx mice showed higher levels of creatine phosphokinase and lower muscle strength, in vivo, than mdx mice. Isometric tension of isolated muscle was reduced, but the susceptibility to eccentric contraction was not increased. The slight aggravation of muscle dystrophy observed in mdx mice deprived of parvalbumin cannot explain the severity of the affection observed in xmd dogs and Duchenne dystrophy patients where parvalbumin is constitutively not expressed.
Raymackers
J M
JM
Department of Physiology and Pharmacology, Catholic University of Louvain, B-1200 Brussels, Belgium.
Debaix
H
H
Colson-Van Schoor
M
M
De Backer
F
F
Tajeddine
N
N
Schwaller
B
B
Gailly
P
P
Gillis
J M
JM
D000367:Age Factors; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D003402:Creatine Kinase / Q000097:blood; D003600:Cytosol / Q000378:metabolism; D016189:Dystrophin / Q000172:deficiency*; D005355:Fibrosis / Q000503:physiopathology; D007537:Isometric Contraction; D051379:Mice; D018101:Mice, Inbred mdx; D018656:Muscle Fibers, Fast-Twitch / Q000473:pathology; D018485:Muscle Fibers, Skeletal / Q000473:pathology; D018482:Muscle, Skeletal / Q000473:pathology* / Q000503:physiopathology*; D009136:Muscular Dystrophies / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D020388:Muscular Dystrophy, Duchenne / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D009154:Mutation; D018995:Myosin Heavy Chains; D010320:Parvalbumins / Q000172:deficiency*; D010641:Phenotype; D013997:Time Factors
D016189:Dystrophin; D010320:Parvalbumins; D003402:Creatine Kinase; D018995:Myosin Heavy Chains; D002118:Calcium