Mouse Genome Informatics
hm
    Epb4.2tm1Llp/Epb4.2tm1Llp
involves: 129P2/OlaHsd * C57BL/6J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
       
hematopoietic system
• mutant RBCs show loss of membrane surface, as shown by significantly reduced osmotic deformability indices; in contrast, the membrane skeleton architecture is intact, and the spectrin and ankyrin content of RBCs is unaffected
• mutant RBCs show a 30% reduction in band 3 content, a ~40% decrease in net DIDS-sensitive sulfate influx, as well as loss and clustering of intramembranous particles
• homozygotes display a population of small and dehydrated RBCs in whole blood
• adult homozygotes exhibit significantly reduced RBC counts relative to wild-type mice
• in contrast, white cell counts, platelet counts, and bleeding times remain unaffected
• adult homozygotes exhibit significantly reduced hematocrits relative to wild-type mice
• adult homozygotes display slightly reduced hemoglobin levels relative to wild-type mice
• adult homozygotes display an elevated MCHC relative to wild-type mice
• adult homozygotes exhibit a reduced MCV relative to wild-type mice
• mutant RBCs display mild hereditary spherocytosis as a result of band 3 deficiency: lipid anchoring is impaired and unsupported lipids lost
• adult homozygotes exhibit a 2-fold increase in reticulocyte percentage
• adult homozygotes are slightly anemic
• increased accumulation of iron in the spleen, indicating RBC damage
• no iron deposition is noted in the kidney, indicating absence of intravascular hemolysis
• adult homozygotes show a 2-fold increase in spleen weight

homeostasis/metabolism
• mutant RBCs show altered cation content (increased K+/decreased Na+) resulting in dehydration
• mutant RBCs show altered cation content (increased K+/decreased Na+) leading to dehydration
• passive Na+ permeability and the activities of the Na-K-2Cl and K-Cl cotransporters, the Na/H exchanger, and the Gardos channel are significantly increased; increased passive Na+ permeability is dependent on cell shrinkage
• notably, cell shrinkage induces a greater activation of Na/H exchange and Na-K-2Cl cotransport in mutant RBCs
• increased accumulation of iron in the spleen, indicating RBC damage
• no iron deposition is noted in the kidney, indicating absence of intravascular hemolysis

immune system
• increased accumulation of iron in the spleen, indicating RBC damage
• no iron deposition is noted in the kidney, indicating absence of intravascular hemolysis
• adult homozygotes show a 2-fold increase in spleen weight

Mouse Models of Human Disease
OMIM IDRef(s)
Spherocytosis, Type 1; SPH1 182900 J:67412