| First Author | Chen Q | Year | 2012 |
| Journal | Blood Cells Mol Dis | Volume | 48 |
| Issue | 2 | Pages | 91-101 |
| PubMed ID | 22260787 | Mgi Jnum | J:270131 |
| Mgi Id | MGI:6276769 | Doi | 10.1016/j.bcmd.2011.12.002 |
| Citation | Chen Q, et al. (2012) A transgenic mouse model expressing exclusively human hemoglobin E: indications of a mild oxidative stress. Blood Cells Mol Dis 48(2):91-101 |
| abstractText | Hemoglobin (Hb) E (beta26 Glu-->Lys) is the most common abnormal hemoglobin (Hb) variant in the world. Homozygotes for HbE are mildly thalassemic as a result of the alternate splice mutation and present with a benign clinical picture (microcytic and mildly anemic) with rare clinical symptoms. Given that the human red blood cell (RBC) contains both HbE and excess alpha-chains along with minor hemoglobins, the consequence of HbE alone on RBC pathophysiology has not been elucidated. This becomes critical for the highly morbid beta(E)-thalassemia disease. We have generated transgenic mice exclusively expressing human HbE (HbEKO) that exhibit the known aberrant splicing of beta(E) globin mRNA, but are essentially non-thalassemic as demonstrated by RBC alpha/beta (human) globin chain synthesis. These mice exhibit hematological characteristics similar to presentations in human EE individuals: microcytic RBC with low MCV and MCH but normal MCHC; target RBC; mild anemia with low Hb, HCT and mildly elevated reticulocyte levels and decreased osmotic fragility, indicating altered RBC surface area to volume ratio. These alterations are correlated with a mild RBC oxidative stress indicated by enhanced membrane lipid peroxidation, elevated zinc protoporphyrin levels, and by small but significant changes in cardiac function. The C57 (background) mouse and full KO mouse models expressing HbE with the presence of HbS or HbA are used as controls. In select cases, the HbA full KO mouse model is compared but found to be limited due to its RBC thalassemic characteristics. Since the HbEKO mouse RBC lacks an abundance of excess alpha-chains that would approximate a mouse thalassemia (or a human thalassemia), the results indicate that the observed in vivo RBC mild oxidative stress arises, at least in part, from the molecular consequences of the HbE mutation. |
