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A transgenic mouse model of hemoglobin S Antilles disease
RA Popp, DM Popp, SG Shinpock, MY Yang, JG Mural, MP Aguinaga, P Kopsombut, PD Roa, EA Turner and EM Rubin
Biology Division, Oak Ridge National Laboratory, TN 37831, USA.
Hemoglobin (Hb) S Antilles is a naturally occurring form of sickling human
Hb but causes a more severe phenotype than Hb S. Two homozygous viable Hb S
Antilles transgene insertions from Tg58Ru and Tg98Ru mice were bred into
MHOAH mice that express high oxygen affinity (P50 approximately 24.5 mm Hg)
rather than normal (P50 approximately 40 mm Hg) mouse Hbs. The rationale
was that the high oxygen affinity MHOAH Hb, the lower oxygen affinity of Hb
S Antilles than Hb S (P50 approximately 40 v 26.5 mm Hg), and the lower
solubility of deoxygenated Hb S Antilles than Hb S (approximately 11 v 18
g/dL) would favor deoxygenation and polymerization of human Hb S Antilles
in MHOAH mouse red blood cells (RBCs). The Tg58 x Tg98 mice produced have a
high and balanced expression (approximately 50% each) of h alpha and h
beta(S Antilles) globins, 25% to 35% of their RBCs are misshapen in vivo,
and in vitro deoxygenation of their blood induces 30% to 50% of the RBCs to
form classical looking, elongated sickle cells with pointed ends. Tg58 x
Tg98 mice exhibit reticulocytosis, an elevated white blood cell count and
lung and kidney pathology commonly found in sickle cell patients, which
should make these mice useful for experimental studies on possible
therapeutic intervention of sickle cell disease.
Volume 89,
Issue 11,
pp. 4204-4212,
06/01/1997
Copyright © 1997 by The American Society of Hematology
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