Analysis Tools
hematopoietic system
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• at 6 weeks of age, homozygotes exhibit splenomegaly due to congestion of the red pulp with hemosiderin accumulation
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• at 8 weeks of age or later, homozygotes show a 1.5-fold increase in the spleen weight per body weight ratio relative to wild-type littermates
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• homozygotes exhibit hemolytic anemia
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• in response to hemolytic anemia, homozygotes display a 1.4-fold increase in the ratio of erythroid to myeloid cells in the bone marrow (33% vs 23% in wild-type mice)
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• at 8 weeks of age, homozygotes exhibit a higher number of normoblasts in the bone marrow than wild-type mice
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• homozygotes exhibit increased dense fractions relative to wild-type mice, indicating the presence of damaged RBCs
• abnormally shaped RBCs are increased in all seven dense fractions obtained from mutant mice and include spherocytes, burr cells, schistocytes, and polychromatophilic macrocytes in the first to second, third to fifth, third to fifth, and the sixth to seventh fractions, respectively
• importantly, the reactive oxygen species (ROS) level in the third to sixth dense fractions is 3- to 9-fold higher in mutant mice relative to wild-type mice
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• in response to hemolytic anemia, homozygotes show a 2-fold increase in serum erythropoietin (EPO) levels at 8 weeks of age
• however, the number of red blood cells (RBCs), mean cell volume (MCV), mean corpuscular hemoglobin (MCH), and white blood cells (WBCs) remain unaffected, and monovalent cation contents (K+ and Na+) of RBCs are not increased significantly in mutant versus wild-type mice
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echinocytosis
(
J:84271
)
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• burr erythrocytes are detected in the third to fifth dense RBC fractions of mutant but not wild-type mice
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• Heinz bodies (i.e. precipitates of denatured globin) are detected in the peripheral blood of homozygotes at 2 weeks of age and account for ~30% of mutant RBCs at 5 weeks of age, but are absent from wild-type blood
• the rate of Heinz body formation in RBCs of splenectomized homozygotes is similar to that of unsplenectomized homozygotes
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• schistocytes are detected in the third to fifth dense RBC fractions of mutant but not wild-type mice
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spherocytosis
(
J:84271
)
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• spherocytes are detected in the first to second dense RBC fractions of mutant but not wild-type mice
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• at 8 weeks of age or later, homozygotes show a dramatic increase in the spleen red pulp
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cellular
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• labeling experiments using the thiol-modifying reagent biotinylated iodoacetamide (BIAM) indicate that various RBC membrane proteins containing low acid constant cysteine residues are highly oxidized in mutant mice, thus placing mutant RBCs at risk for hemolysis
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• in response to H2O2 treatment, mutant RBCs exhibit a 2-fold increase in levels of methemoglobin (an oxidant of hemoglobin) relative to wild-type RBCs, indicating increased sensitivity to oxidant stress
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homeostasis/metabolism
hemosiderosis
(
J:84271
)
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• at 8 weeks of age or later, homozygotes display accumulation of hemosiderin in spleen
• at 8 weeks of age, hemosiderin is significantly increased within the Kupffer cells of livers of splenectomized homozygotes but is scant in livers of unsplectomized homozygotes and absent from the livers of splenectomized wild-type mice
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immune system
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• at 6 weeks of age, homozygotes exhibit splenomegaly due to congestion of the red pulp with hemosiderin accumulation
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• at 8 weeks of age or later, homozygotes show a 1.5-fold increase in the spleen weight per body weight ratio relative to wild-type littermates
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• at 8 weeks of age or later, homozygotes show a dramatic increase in the spleen red pulp
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growth/size/body
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• at 6 weeks of age, homozygotes exhibit splenomegaly due to congestion of the red pulp with hemosiderin accumulation
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• at 8 weeks of age or later, homozygotes show a 1.5-fold increase in the spleen weight per body weight ratio relative to wild-type littermates
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