title: In vivo and in vitro investigations of heterozygous nebulin knock-out mice disclose a mild skeletal muscle phenotype.
abstract: Nemaline myopathy is the most common congenital skeletal muscle disease, and mutations in the nebulin gene account for 50% of all cases. Recent studies suggest that the disease severity might be related to the nebulin expression levels. Considering that mutations in the nebulin gene are typically recessive, one would expect that a single functional nebulin allele would maintain nebulin protein expression which would result in preserved skeletal muscle function. We investigated skeletal muscle function of heterozygous nebulin knock-out (i.e., nebulin(+/-)) mice using a multidisciplinary approach including protein and gene expression analysis and combined in vivo and in vitro force measurements. Skeletal muscle anatomy and energy metabolism were studied strictly non-invasively using magnetic resonance imaging and 31P-magnetic resonance spectroscopy. Maximal force production was reduced by around 16% in isolated muscle of nebulin(+/-) mice while in vivo force generating capacity was preserved. Muscle weakness was associated with a shift toward a slower proteomic phenotype, but was not related to nebulin protein deficiency or to an impaired energy metabolism. Further studies would be warranted in order to determine the mechanisms leading to a mild skeletal muscle phenotype resulting from the expression of a single nebulin allele.
authors: Aix-Marseille Université, CRMBM, 13005 Marseille, France.
authors: C
authors: C
authors: Gineste
authors: J M
authors: JM
authors: De Winter
authors: C
authors: C
authors: Kohl
authors: C C
authors: CC
authors: Witt
authors: B
authors: B
authors: Giannesini
authors: K
authors: K
authors: Brohm
authors: Y
authors: Y
authors: Le Fur
authors: N
authors: N
authors: Gretz
authors: C
authors: C
authors: Vilmen
authors: E
authors: E
authors: Pecchi
authors: M
authors: M
authors: Jubeau
authors: P J
authors: PJ
authors: Cozzone
authors: G J M
authors: GJ
authors: Stienen
authors: H
authors: H
authors: Granzier
authors: S
authors: S
authors: Labeit
authors: C A C
authors: CA
authors: Ottenheijm
authors: D
authors: D
authors: Bendahan
authors: J
authors: J
authors: Gondin
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D015870:Gene Expression; D006579:Heterozygote; D066298:In Vitro Techniques; D008279:Magnetic Resonance Imaging; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009124:Muscle Proteins / Q000235:genetics* / Q000502:physiology; D053580:Muscle Strength; D018908:Muscle Weakness / Q000235:genetics* / Q000503:physiopathology; D018482:Muscle, Skeletal / Q000502:physiology* / Q000503:physiopathology; D009154:Mutation; D017696:Myopathies, Nemaline / Q000235:genetics* / Q000503:physiopathology; D010641:Phenotype; D012720:Severity of Illness Index
chemical_list: D009124:Muscle Proteins; C035620:nebulin