title: Myonuclear degeneration in LMNA null mice.
abstract: Lamins A/C, the major constituent of the nuclear lamina, confer mechanical stability to nuclei. We examined the myonuclei of LMNA null mice at the myotendinous junctions (MTJ), the site of longitudinal force transmission from contractile proteins to extracellular proteins. The right soleus and rectus femoris muscles of five null mutants aged 5-7 weeks and two wild-type animals aged 5 weeks and 6 months were examined by electron microscopy. The myofibers merging into the tendons were assessed for nuclear disintegration and cytoplasmic degeneration. The myofibers of the wild-type rectus femoris and soleus muscles revealed 19-27 nuclei/50 myofibers and 5-8/20, respectively, with no signs of degeneration. The rectus femoris muscle fibers of the null mice contained 75-117 myonuclei/50 myofibers, the soleus muscle, 13-36 nuclei/20 myofibers. Eleven to twenty-one per 50 myonuclei of the rectus femoris myonuclei showed chromatin clumping, nuclear fragmentation, nuclear inclusions and invaginations, and intranuclear filaments. The values were 12-19/50 for the soleus myonuclei. Moreover, 5-12/50 rectus femoris myofibers and 5-14/20, of the soleus myofibers showed cytoplasmic degeneration. None of these changes was found distal to the MTJ. These results favor the notion that myonuclei lacking a functional lamina are susceptible to mechanical stress in vivo. These alterations may contribute to the development of early joint contractures, a feature of ADEDMD.
authors: Institute of Neuropathology, University Hospital of Zürich, Switzerland.
authors: Michel
authors: M
authors: Mittelbronn
authors: Teresa
authors: T
authors: Sullivan
authors: Colin L
authors: CL
authors: Stewart
authors: Antje
authors: A
authors: Bornemann
mesh_terms: D000818:Animals; D002467:Cell Nucleus / Q000648:ultrastructure*; D004195:Disease Models, Animal; D034904:Lamin Type A / Q000235:genetics*; D051379:Mice; D018345:Mice, Knockout; D046529:Microscopy, Electron, Transmission; D018485:Muscle Fibers, Skeletal / Q000648:ultrastructure*; D018482:Muscle, Skeletal / Q000648:ultrastructure*; D009137:Muscular Dystrophy, Animal / Q000235:genetics / Q000473:pathology*; D020389:Muscular Dystrophy, Emery-Dreifuss / Q000235:genetics / Q000473:pathology
chemical_list: D034904:Lamin Type A