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Prepublished online as a Blood First Edition Paper on July 5, 2002; DOI 10.1182/blood-2002-05-1409.
Submitted May 14, 2002
Accepted June 18, 2002
Deletion of the mouse  globin regulatory element (HS -26) has an unexpectedly mild phenotype
Edouardo Anguita, Jacqueline A Sharpe, Jacqueline A Sloane-Stanley, Christina Tufarelli, Douglas R Higgs, and William G Wood*
MRC Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United Kingdom
* Corresponding author; email: bwood{at}hammer.imm.ox.ac.uk.
Natural deletions of the region upstream of the human globin gene cluster, together with expression studies in cell lines and transgenic mice, have identified a single element (HS -40) as necessary and perhaps sufficient for high level expression of the -globin genes. A similar element occupies the corresponding position upstream of the mouse -globin genes (mHS -26) and was thought to have similar functional properties. We have knocked out mHS -26 by homologous recombination with the surprising result that instead of the expected severe thalassemia phenotype, these mice have a mild disease. Transcription levels of the mouse genes were reduced by ~50% but homozygotes were healthy with normal hemoglobin levels and only mild decreases in MCV and MCH. These results may point to differences in the regulation of the globin clusters in the two species or indicate that additional cis acting elements remain to be characterised in one or both clusters.
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