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Prepublished online as a Blood First Edition Paper on July 5, 2002; DOI 10.1182/blood-2002-05-1409.
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Blood, 15 November 2002, Vol. 100, No. 10, pp. 3450-3456
PLENARY PAPER
Deletion of the mouse  -globin regulatory element
(HS  26) has an unexpectedly mild phenotype
Eduardo Anguita,
Jacqueline
A. Sharpe,
Jacqueline A. Sloane-Stanley,
Cristina Tufarelli,
Douglas R. Higgs, and
William G. Wood
From the Medical Research Council Molecular Haematology
Unit, Weatherall Institute of Molecular Medicine, University of Oxford,
United Kingdom.
Natural deletions of the region upstream of the human
 -globin gene cluster, together with expression studies in cell lines and transgenic mice, 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 (m) -globin genes (mHS 26) and was
thought to have similar functional properties. We knocked out mHS 26
by homologous recombination and observed the surprising result that
instead of the expected severe -thalassemia phenotype, the mice had
a mild disease. Transcription levels of the mouse genes were reduced by
about 50%, but homozygotes were healthy, with normal hemoglobin levels
and only mild decreases in mean corpuscular volume and mean corpuscular
hemoglobin. These results may indicate differences in the regulation of
the -globin clusters in mice and humans or that additional
cis-acting elements remain to be characterized in one or
both clusters.
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