RGD Reference Report - Mutation in erythroid specific transcription factor KLF1 causes Hereditary Spherocytosis in the Nan hemolytic anemia mouse model. - Rat Genome Database

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Mutation in erythroid specific transcription factor KLF1 causes Hereditary Spherocytosis in the Nan hemolytic anemia mouse model.

Authors: Heruth, DP  Hawkins, T  Logsdon, DP  Gibson, MI  Sokolovsky, IV  Nsumu, NN  Major, SL  Fegley, B  Woods, GM  Lewing, KB  Neville, KA  Cornetta, K  Peterson, KR  White, RA 
Citation: Heruth DP, etal., Genomics. 2010 Nov;96(5):303-7. doi: 10.1016/j.ygeno.2010.07.009. Epub 2010 Aug 5.
RGD ID: 10769342
Pubmed: (View Article at PubMed) PMID:20691777
DOI: Full-text: DOI:10.1016/j.ygeno.2010.07.009

KLF1 regulates definitive erythropoiesis of red blood cells by facilitating transcription through high affinity binding to CACCC elements within its erythroid specific target genes including those encoding erythrocyte membrane skeleton (EMS) proteins. Deficiencies of EMS proteins in humans lead to the hemolytic anemia Hereditary Spherocytosis (HS) which includes a subpopulation with no known genetic defect. Here we report that a mutation, E339D, in the second zinc finger domain of KLF1 is responsible for HS in the mouse model Nan. The causative nature of this mutation was verified with an allelic test cross between Nan/+ and heterozygous Klf1(+/-) knockout mice. Homology modeling predicted Nan KLF1 binds CACCC elements more tightly, suggesting that Nan KLF1 is a competitive inhibitor of wild-type KLF1. This is the first association of a KLF1 mutation with a disease state in adult mammals and also presents the possibility of being another causative gene for HS in humans.

Annotation

Disease Annotations    

Objects Annotated

Genes (Rattus norvegicus)
Klf1  (Kruppel like factor 1)

Genes (Mus musculus)
Klf1  (Kruppel-like factor 1 (erythroid))

Genes (Homo sapiens)
KLF1  (Kruppel like factor 1)


Additional Information