RRC ID 18916
Author Shigemura T, Shiohara M, Tanaka M, Takeuchi K, Koike K.
Title Effect of the mutant microphthalmia-associated transcription factor found in Tietz syndrome on the in vitro development of mast cells.
Journal J. Pediatr. Hematol. Oncol.
Abstract SUMMARY:Mutations in microphthalmia-associated transcription factor (MITF) lead to Waardenburg syndrome type 2 (WS2), a dominantly inherited disorder involving hearing loss and pigment disturbances caused by a lack of melanocytes. On rare occasions, mutations in MITF lead to Tietz syndrome (TS), which is characterized by a severe WS2 phenotype. The MITF gene is the human homolog of the mouse microphthalmia (mi) gene in some families. Mi/mi mice show decreased numbers and an abnormal phenotype of mast cells (MC). In contrast, the number and phenotype of MC in WS2/TS patients who also have an alteration in their MITF gene are unclear. In this study, we identified a mutation in the MITF gene, delR217, which was equivalent to that found in mi/mi mice, in a case of TS. None of the MITF isoforms with the mutation were able to transactivate the tyrosinase gene promoter. In addition, mutant MITF-M showed dominant negative activity toward wild-type MITF-M, inhibiting its transactivation of the tyrosinase gene promoter. The patient's peripheral blood CD34 cells showed no differences with respect to total cell number or their expression levels of tryptase mRNA in a serum-deprived liquid culture system for 6 weeks when compared with normal control cells. These findings suggest that MITF does not play a critical role in MC development in humans.
Volume 32(6)
Pages 442-7
Published 2010-8
DOI 10.1097/MPH.0b013e3181d9da5d
PMID 20485200
MeSH Adolescent Antigens, CD34 / metabolism Cell Differentiation / genetics* Cell Separation Female Flow Cytometry Humans Immunohistochemistry In Vitro Techniques Male Mast Cells / cytology* Mast Cells / metabolism Microphthalmia-Associated Transcription Factor / genetics* Microphthalmia-Associated Transcription Factor / metabolism Monophenol Monooxygenase / biosynthesis Monophenol Monooxygenase / genetics Mutation Pedigree Promoter Regions, Genetic Reverse Transcriptase Polymerase Chain Reaction Transcriptional Activation Waardenburg Syndrome / genetics* Waardenburg Syndrome / metabolism
IF 0.947
Times Cited 2
Human and Animal Cells 293T (RCB2202)