| First Author | Siatecka M | Year | 2010 |
| Journal | Proc Natl Acad Sci U S A | Volume | 107 |
| Issue | 34 | Pages | 15151-6 |
| PubMed ID | 20696915 | Mgi Jnum | J:163685 |
| Mgi Id | MGI:4829428 | Doi | 10.1073/pnas.1004996107 |
| Citation | Siatecka M, et al. (2010) Severe anemia in the Nan mutant mouse caused by sequence-selective disruption of erythroid Kruppel-like factor. Proc Natl Acad Sci U S A 107(34):15151-6 |
| abstractText | Studies of mouse models of anemia have long provided fundamental insights into red blood cell formation and function. Here we show that the semidominant mouse mutation Nan ('neonatal anemia') carries a single amino acid change (E339D) within the second zinc finger of the erythroid Kruppel-like factor (EKLF), a critical erythroid regulatory transcription factor. The mutation alters the DNA-binding specificity of EKLF so that it no longer binds promoters of a subset of its DNA targets. Remarkably, even when mutant Nan and wild-type EKLF alleles are expressed at equivalent levels, the mutant form selectively interferes with expression of EKLF target genes whose promoter elements it no longer binds. This interference yields a distorted genetic output and selective protein deficiencies that differ from those seen in EKLF-heterozygous and EKLF-null red blood cells and presents a unique and unexpected mechanism of inherited disease. |
