| First Author | Leder A | Year | 1997 |
| Journal | Blood | Volume | 90 |
| Issue | 3 | Pages | 1275-82 |
| PubMed ID | 9242562 | Mgi Jnum | J:41934 |
| Mgi Id | MGI:894846 | Doi | 10.1182/blood.v90.3.1275.1275_1275_1282 |
| Citation | Leder A, et al. (1997) Mouse zeta- and alpha-globin genes: Embryonic survival, alpha-thalassemia, and genetic background effects. Blood 90(3):1275-1282 |
| abstractText | A classical notion regarding the expression of murine embryonic zeta- and adult alpha-globin genes holds that there is a switch in globin production from the embryonic to the adult form during fetal development. Our previous in situ hybridization studies challenged this view, since both zeta- and alpha-globin mRNAs can be detected simultaneously in the earliest erythrocyte populations, This finding raises the possibility that zeta-globin production might be wholly or partially redundant in embryos in which the adult alpha-globin is also expressed. To test this possibility, we created a null mutation of the zeta-globin gene using homologous recombination in embryonic stem cells. Many outbred mice homozygous for the zeta-null mutation were able to develop normally, undermining the notion that there is an absolute need for zeta-globin and indicating that alpha-globin alone can serve the survival needs of the fetus. Interestingly, insertion of the PGK-Neo cassette (used to create the null mutation) into the zeta-globin gene appears to influence the expression of the nearby alpha-globin genes, giving rise to reduced alpha-globin production and to an alpha- thalassemia-like syndrome. There is also evidence indicating the strong influence of genetic background on the zeta-null and alpha 1-null phenotypes, both of which are much more severe in the 129/SvEv inbred genetic background. These quantitative differences can potentially be exploited to identify genes important for erythropoiesis. (C) 1997 by The American Society of Hematology. |
