Mutation in erythroid specific transcription factor KLF1 causes Hereditary Spherocytosis in the Nan hemolytic anemia mouse model
| Autor: | Karen B. Lewing, Kathleen A. Neville, Inna Sokolovsky, Ndona N. Nsumu, Daniel P. Heruth, Derek P. Logsdon, Margaret Gibson, Robert A. White, Troy Hawkins, Stephanie L. Major, Kenneth Cornetta, Barbara Fegley, Gerald M. Woods, Kenneth R. Peterson |
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| Rok vydání: | 2010 |
| Předmět: |
Hemolytic anemia
Anemia Hemolytic Mutant Spherocytosis Kruppel-Like Transcription Factors KLF1 Spherocytosis Hereditary Biology Article Hereditary spherocytosis Mice 03 medical and health sciences 0302 clinical medicine Genetics medicine Animals Humans Transcription factor 030304 developmental biology Mice Knockout Zinc finger 0303 health sciences Zinc Fingers medicine.disease Mice Inbred C57BL Disease Models Animal 030220 oncology & carcinogenesis Mutation Erythropoiesis |
| Zdroj: | Genomics. 96:303-307 |
| ISSN: | 0888-7543 |
| DOI: | 10.1016/j.ygeno.2010.07.009 |
| Popis: | Article history:Received 3 February 2010Accepted 28 July 2010Available online 5 August 2010Keywords:Hereditary SpherocytosisAnemiaKLF1EKLFMouse mutant KLF1 regulates definitive erythropoiesis of red blood cells by facilitating transcription through high affinitybinding to CACCC elements within its erythroid specific target genes including those encoding erythrocytemembrane skeleton (EMS) proteins. Deficiencies of EMS proteins in humans lead to the hemolytic anemiaHereditary Spherocytosis (HS) which includes a subpopulation with no known genetic defect. Here wereport that a mutation, E339D, in the second zinc finger domain of KLF1 is responsible for HS in the mousemodel Nan. The causative nature of this mutation was verified with an allelic test cross between Nan/+ andheterozygous Klf1 +/− knockout mice. Homology modeling predicted Nan KLF1 binds CACCC elements moretightly, suggesting that Nan KLF1 is a competitive inhibitor of wild-type KLF1. This is the first association of aKLF1 mutation with a disease state in adult mammals and also presents the possibility of being anothercausative gene for HS in humans.© 2010 Elsevier Inc. All rights reserved. |
| Databáze: | OpenAIRE |
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