The role of membrane skeletal-associated alpha-globin in the
pathophysiology of beta-thalassemia
S Sorensen, E Rubin, H Polster, N Mohandas and S Schrier
University of California, San Francisco.
The beta-thalassemic mouse provides a useful model for testing hypotheses
about the pathophysiology in human beta-thalassemia. The clinical picture
of these mice and their red blood cell deformability characteristics are
quite similar to those observed in human beta- thalassemia intermedia. The
creation of transgenic mice that express human beta-globin (beta s) has
provided an opportunity to study the effect of increasing the
non-alpha-globin chain production on the thalassemic phenotype. A small
increase in beta-globin production produces transgenic mice that are
healthier, have almost normal hemoglobin values, and whose red blood cell
deformability is increased. We quantified and characterized the membrane
skeletal-associated globin in normal, transgenic thal/sickle, and
thalassemic mice and showed that only alpha-globin was associated with the
membrane skeleton in the pathologic red blood cells, and that the degree of
rigidity as measured in the rheoscope correlated directly and closely with
the amount of membrane skeletal-associated globin in these abnormal red
blood cells.
Volume 75,
Issue 6,
pp. 1333-1336,
03/15/1990
Copyright © 1990 by The American Society of Hematology
