title: Correlation between the clinical phenotype of MYH9-related disease and tissue distribution of class II nonmuscle myosin heavy chains.
abstract: Nonmuscle myosin heavy chain II-A is responsible for MYH9-related disease, which is characterized by macrothrombocytopenia, granulocyte inclusions, deafness, cataracts, and renal failure. Since another two highly conserved nonmuscle myosins, II-B and II-C, are known, an analysis of their tissue distribution is fundamental for the understanding of their biological roles. In mouse, we found that all forms are ubiquitously expressed. However, megakaryocytic and granulocytic lineages express only II-A, suggesting that congenital features, macrothrombocytopenia, and leukocyte inclusions correlate with its exclusive presence. In kidney, eye, and ear, where clinical manifestations have a late onset, as well as in other tissues apparently not affected in patients, II-A and at least one of the other two isoforms are expressed, suggesting that II-B and II-C can partially compensate for each other. We hypothesize that cells expressing only II-A manifest the congenital defects, while tissues expressing additional myosin II isoforms show either late onset of abnormalities or no pathological sign.
authors.affiliation: Telethon Institute of Genetics and Medicine, Via Pietro Castellino, 111, 80131 Naples, Italy.
authors.forename: Valeria
authors.initials: V
authors.lastname: Marigo
authors.forename: Alessandra
authors.initials: A
authors.lastname: Nigro
authors.forename: Alessandro
authors.initials: A
authors.lastname: Pecci
authors.forename: Donatella
authors.initials: D
authors.lastname: Montanaro
authors.forename: Mariateresa
authors.initials: M
authors.lastname: Di Stazio
authors.forename: Carlo L
authors.initials: CL
authors.lastname: Balduini
authors.forename: Anna
authors.initials: A
authors.lastname: Savoia
mesh_terms: D000818:Animals; D001853:Bone Marrow / Q000378:metabolism / Q000648:ultrastructure; D002386:Cataract / Q000235:genetics; D003051:Cochlea / Q000378:metabolism / Q000648:ultrastructure; D003638:Deafness / Q000235:genetics; D004622:Embryo, Mammalian / Q000378:metabolism / Q000648:ultrastructure; D005123:Eye / Q000378:metabolism / Q000648:ultrastructure; D015870:Gene Expression; D006098:Granulocytes / Q000648:ultrastructure; D006801:Humans; D017403:In Situ Hybridization; D002479:Inclusion Bodies / Q000235:genetics; D007668:Kidney / Q000378:metabolism / Q000648:ultrastructure; D008099:Liver / Q000378:metabolism / Q000648:ultrastructure; D051379:Mice; D020409:Molecular Motor Proteins / Q000235:genetics*; D018995:Myosin Heavy Chains / Q000235:genetics* / Q000378:metabolism*; D024462:Myosin Type II / Q000235:genetics / Q000378:metabolism*; D009393:Nephritis / Q000235:genetics; D010641:Phenotype; D012333:RNA, Messenger / Q000032:analysis; D013577:Syndrome; D013921:Thrombocytopenia / Q000175:diagnosis / Q000235:genetics*; D014018:Tissue Distribution
chemical_list: C103814:MYH9 protein, human; D020409:Molecular Motor Proteins; D012333:RNA, Messenger; D024462:Myosin Type II; D018995:Myosin Heavy Chains