PMID- 2612906 OWN - NLM STAT- MEDLINE DCOM- 19900301 LR - 20190516 IS - 0890-9369 (Print) IS - 0890-9369 (Linking) VI - 3 IP - 10 DP - 1989 Oct TI - High-level, erythroid-specific expression of the human alpha-globin gene in transgenic mice and the production of human hemoglobin in murine erythrocytes. PG - 1572-81 AB - Using the dominant control region (DCR) sequences that flank the beta-globin gene locus, we have been able to achieve high-level expression of the human alpha-globin gene in transgenic mice. Expression in fetal liver and blood is copy number dependent and at levels comparable to that of the endogenous mouse alpha-globin genes. Transgenic fetuses with high-copy numbers of the transgene suffer severe anemia and die before birth. Using a construct with both the human alpha- and beta-globin genes and the beta-globin DCR, live mice with low-copy numbers were obtained. Both human globin genes are expressed at high levels in adult red cells to give human hemoglobin HbA in amounts equal to or greater than endogenous mouse hemoglobin. Expression of HbA in murine red cells is not accompanied by any increase in mean corpuscular volume (MCV) or mean corpuscular hemoglobin concentration (MCHC). However, these transgenic mice tend to have an increased number of reticulocytes in peripheral blood; consistent with some degree of hemolysis. Metabolic labeling experiments showed balanced mouse globin synthesis, but imbalanced human globin synthesis, with an alpha/beta biosynthetic ratio of approximately 0.6. Thus, these mice have mild anemia. These results are discussed with relation to the coordinate regulation of alpha- and beta-globin synthesis in erythroid tissues. FAU - Hanscombe, O AU - Hanscombe O AD - Laboratory of Gene Structure and Expression, National Institute for Medical Research, London, UK. FAU - Vidal, M AU - Vidal M FAU - Kaeda, J AU - Kaeda J FAU - Luzzatto, L AU - Luzzatto L FAU - Greaves, D R AU - Greaves DR FAU - Grosveld, F AU - Grosveld F LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Genes Dev JT - Genes & development JID - 8711660 RN - 9004-22-2 (Globins) RN - 9034-51-9 (Hemoglobin A) SB - IM MH - Animals MH - Blotting, Southern MH - Erythrocytes/metabolism MH - *Gene Expression MH - Globins/biosynthesis/*genetics MH - Hemoglobin A/biosynthesis/*genetics MH - Hemoglobinopathies/genetics MH - Humans MH - In Vitro Techniques MH - Isoelectric Focusing MH - Mice MH - Mice, Transgenic EDAT- 1989/10/01 00:00 MHDA- 1989/10/01 00:01 CRDT- 1989/10/01 00:00 PHST- 1989/10/01 00:00 [pubmed] PHST- 1989/10/01 00:01 [medline] PHST- 1989/10/01 00:00 [entrez] AID - 10.1101/gad.3.10.1572 [doi] PST - ppublish SO - Genes Dev. 1989 Oct;3(10):1572-81. doi: 10.1101/gad.3.10.1572.