title: The distribution of SMN protein complex in human fetal tissues and its alteration in spinal muscular atrophy.
abstract: Spinal muscular atrophy (SMA) is a common autosomal recessive neuromuscular disorder characterized by degeneration of motor neurons of the spinal cord and muscular atrophy. SMA is caused by alterations to the survival of motor neuron (SMN) gene, the function of which has hitherto been unclear. Here, we present immunoblot analyses showing that normal SMN protein expression undergoes a marked decay in the postnatal period compared with fetal development. Morphological and immunohistochemical analyses of the SMN protein in human fetal tissues showed a general distribution in the cytoplasm, except in muscle cells, where SMN protein was immunolocalized to large cytoplasmic dot-like structures and was tightly associated with membrane-free heavy sedimenting complexes. These cytoplasmic structures were similar in size to gem. The SMN protein was markedly deficient in tissues derived from type I SMA fetuses, including skeletal muscles and, as previously shown, spinal cord. While our data do not help decide whether SMA results from impaired SMN expression in spinal cord, skeletal muscle or both, they suggest a requirement for SMN protein during embryo-fetal development.
authors.affiliation: Unité de Recherches sur les Handicaps Génétiques de l'Enfant, INSERM Unité 393, IFREM, France.
authors.forename: P
authors.initials: P
authors.lastname: Burlet
authors.forename: C
authors.initials: C
authors.lastname: Huber
authors.forename: S
authors.initials: S
authors.lastname: Bertrandy
authors.forename: M A
authors.initials: MA
authors.lastname: Ludosky
authors.forename: I
authors.initials: I
authors.lastname: Zwaenepoel
authors.forename: O
authors.initials: O
authors.lastname: Clermont
authors.forename: J
authors.initials: J
authors.lastname: Roume
authors.forename: A L
authors.initials: AL
authors.lastname: Delezoide
authors.forename: J
authors.initials: J
authors.lastname: Cartaud
authors.forename: A
authors.initials: A
authors.lastname: Munnich
authors.forename: S
authors.initials: S
authors.lastname: Lefebvre
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002458:Cell Fractionation; D017362:Cyclic AMP Response Element-Binding Protein; D005260:Female; D005333:Fetus / Q000737:chemistry*; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D018482:Muscle, Skeletal / Q000737:chemistry / Q000196:embryology; D009134:Muscular Atrophy, Spinal / Q000196:embryology / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D011247:Pregnancy; D016601:RNA-Binding Proteins; D055532:SMN Complex Proteins; D013347:Subcellular Fractions / Q000737:chemistry; D014018:Tissue Distribution
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; D009419:Nerve Tissue Proteins; D016601:RNA-Binding Proteins; D055532:SMN Complex Proteins