Analysis Tools
hematopoietic system
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• homozygotes exhibit a significant increase in reticulocyte count relative to wild-type mice
• however, homozygotes are not anemic, and hemoglobin concentration, red cell number, white cell number, and platelet number are within normal range at both ages tested
• at 10 weeks of age, male homozygotes display higher reticulocyte counts than female homozygotes (mean of 5.63% vs 4.23%) and shorter calculated t1/2 (7.9 days vs 10.7 days)
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• in vitro, mutant erythrocytes are much more susceptible in a classical pathway assay to lysis by homologous or heterologous serum than heterozygous or wild-type erythrocytes
• mutant erythrocytes bearing human or rat C5b-7 sites are extremely susceptible to lysis when either rat or mouse serum is provided as a source of terminal C components, whereas similarly treated wild-type cells are resistant
• furthermore, mutant erythrocytes are positive in the acidified serum lysis assay (Ham test), whereas wild-type erythrocytes are negative (i.e. they do not lyse)
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homeostasis/metabolism
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• at 10 weeks of age, homozygotes display spontaneous intravascular hemolysis with a significant rise in mean plasma hemoglobin concentration relative to wild-type mice (12.6 g/L vs 4.8 g/L, respectively), as measured by spectrophotometry at multiple wavelengths
• notably, plasma hemoglobin concentration is significantly higher in male homozygotes than in female homozygotes (14.6 g/L vs 10.6 g/L, respectively), although erythrocytes tested in vitro are equally susceptible to complement lysis
• administration of cobra venom factor (CVF) to male homozygotes causes a further increase in intravascular hemolysis, as shown by a significant rise in plasma hemoglobin concentration at 1 hr after CVF treatment; by contrast, only a modest increase in hemoglobin concentration is observed in CVF-treated female homozygotes
• analysis of plasma hemolytic activities indicate that male homozygotes have significantly higher hemolytic complement activities, providing a putative explanation for the observed sex differences
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• at 8 weeks of age, homozygotes exhibit significant hemoglobinuria, as determined by measuring absorbance at 412 nm
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renal/urinary system
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• at 8 weeks of age, homozygotes exhibit significant hemoglobinuria, as determined by measuring absorbance at 412 nm
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growth/size/body
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• male, but not female, homozygotes are consistently 10% (2 to 3 g in adults) lighter than their wild-type counterparts
• however, both sexes are fully viable, fertile, and otherwise normal up to 30 weeks of age
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