engleski

Morphological analysis of the absence of adducin from the erythrocyte skeleton in ß-adducin deficient mice

Deficiencies or defects in erythrocyte membrane skeletal proteins are associated with a variety of inherited disorders of red blood cell morphology and function (1). Erythrocyte adducin is one of the proteins localized at the spectrin-actin junction of the membrane skeleton (2, 3). In order to get insight in adducin function in erythrocyte we produced the knock out of ß-adducin in mouse. The resulting deficiency of b-adducin depleted as well the a-adducin subunit from the erythrocyte skeleton. The erythrocyte shape was analyzed by scanning electron microscopy and the morphology of spleen by histology and transmission electron microscopy. The absence of adducin modified the shape of erythrocytes. Mild elliptocytosis characterized by rounded elliptocytes (ovalocytes) was found in the b-adducin mutant mice (figure 1). The observed splenomegaly was connected with the extension of the red pulp. The presence of erythroblasts indicated the extramedullary hematopoiesis in the spleen (figure 2). The normal erythrocyte counts, the increased reticulocyte counts and the increased osmotic fragility of erythrocytes were present in the mutant mice. These data suggested that ß-adducin deficient mice suffered from the mild compensated anemia, which corresponds to the human erythrocyte disorder denominated spherocytic hereditary elliptocytosis (1). 1. Palek, J. (1991) in Red cell membrane disorders, eds. Hoffman, R., Benz, E. J., Jr., Furie, B., Shattil, S. & Cohen, H. (Churchill Livingstone, New York), pp. 472-504. 2. Gardner, K. & Bennett, V. (1987) Nature 328, 359-62. 3. Kuhlman, P. A., Hughes, C. A., Bennett, V. & Fowler, V. M. (1996) J Biol Chem 271, 7986-91. Figure 1. Scanning electron micrographs made by Variable Pressure Scanning Electron Microscope SEM LEO 435VP showing normal (A) and mutant (B) native blood smear. Notice the presence of elliptocytes and decreased central concavity in the mutant. Bar 10 ľm. Figure 2. Transmission electron micrograph of the mutant spleen showing the erythroblasts involved in extramedullary erythropoiesis. Bar 10 ľm.

adducin; erythrocyte; cytoskeleton; elliptocytosys

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