| First Author | Nilson DG | Year | 2006 |
| Journal | Exp Hematol | Volume | 34 |
| Issue | 6 | Pages | 705-12 |
| PubMed ID | 16728274 | Mgi Jnum | J:111912 |
| Mgi Id | MGI:3655027 | Doi | 10.1016/j.exphem.2006.02.018 |
| Citation | Nilson DG, et al. (2006) Major erythrocyte membrane protein genes in EKLF-deficient mice. Exp Hematol 34(6):705-12 |
| abstractText | OBJECTIVES: Mice deficient in the transcription factor erythroid Kruppel-like factor, KLF1 (EKLF) die approximately 14.5 days postcoitum of anemia, attributed to decreased expression of the beta-globin gene. The objectives of this study were to rescue EKLF-deficient embryos with mice expressing gamma-globin from beta-spectrin or ankyrin promoters and to characterize expression of the major erythrocyte membrane genes in EKLF-deficient cells. METHODS: Transgenic beta-spectrin/gamma-globin or ankyrin/gamma-globin mice were bred onto EKLF-deficient and wild-type backgrounds. Animals were genotyped, gamma-globin mRNA levels measured, and hemoglobin electrophoresis performed. Steady-state mRNA levels and transcriptional rates of the major erythrocyte membrane protein genes were assayed. RESULTS: beta-spectrin/gamma-globin or ankyrin/gamma-globin mice on EKLF-deficient and wild-type backgrounds had identical levels of gamma-globin mRNA, indicating EKLF-independence of these promoters. gamma-Globin expression improved globin chain imbalance, but hemolysis was not improved and no live-born EKLF-deficient/(A)gamma-globin mice were obtained. Circulating erythroid cells from EKLF-deficient/(A)gamma-globin embryos exhibited hemolysis reminiscent of that seen in patients with severe erythrocyte membrane defects. Levels of beta-spectrin, ankyrin, and band 3 mRNA, but not alpha-spectrin, were decreased in EKLF-deficient fetal liver RNA. In a run-on assay, levels of transcription of the ankyrin and band 3 genes were decreased in EKLF-deficient fetal liver nuclei. CONCLUSIONS: These results indicate that the EKLF-responsive regions of the ankyrin and beta-spectrin genes are outside their promoters and that EKLF is necessary for full transcriptional activity of the ankyrin and band 3 genes; the results also provide additional evidence that defects in addition to beta-globin deficiency, including an abnormal erythrocyte membrane, contribute to the anemia and embryonic lethality in EKLF-deficient mice. |
