title: Transfection of the mutant MYH9 cDNA reproduces the most typical cellular phenotype of MYH9-related disease in different cell lines.
abstract: BACKGROUND
  Heterozygous mutations of MYH9, encoding the Non-Muscular Myosin Heavy Chain-IIA (NMMHC-IIA), cause a complex disorder named MYH9-related disease, characterized by a combination of different phenotypic features. At birth, patients present platelet macrocytosis, thrombocytopenia and leukocyte inclusions containing NMMHC-IIA. Moreover, later in life some of them develop the additional features of sensorineural hearing loss, cataracts and/or glomerulonephritis that sometimes leads to end stage renal failure.
  
  
  RESULTS
  To clarify the mechanism by which the mutant NMMHC-IIA could cause phenotypic anomalies at the cellular level, we examined the effect of transfection of the full-length mutated D1424H MYH9 cDNAs. We have observed, by confocal microscopy, abnormal distribution of the protein and formation of rod-like aggregates reminiscent of the leukocyte inclusions found in patients. Co-transfection of differently labeled wild-type and mutant full-length cDNAs showed the simultaneous presence of both forms of the protein in the intracellular aggregates.
  
  
  CONCLUSIONS
  These findings suggest that the NMMHC-IIA mutated in position 1424 is able to interact with the WT form in living cells, despite part of the mutant protein precipitates in non-functional aggregates. Transfection of the entire WT or mutant MYH9 in cell lines represents a powerful experimental model to investigate consequences of MYH9 mutations.
authors.affiliation: Laboratory of Molecular Genetics, G, Gaslini Institute, Genova, Italy. rravazzo@unige.it.
authors.forename: Emanuele
authors.initials: E
authors.lastname: Panza
authors.forename: Monica
authors.initials: M
authors.lastname: Marini
authors.forename: Alessandro
authors.initials: A
authors.lastname: Pecci
authors.forename: Francesca
authors.initials: F
authors.lastname: Giacopelli
authors.forename: Valeria
authors.initials: V
authors.lastname: Bozzi
authors.forename: Marco
authors.initials: M
authors.lastname: Seri
authors.forename: Carlo
authors.initials: C
authors.lastname: Balduini
authors.forename: Roberto
authors.initials: R
authors.lastname: Ravazzolo