Phenotypes Associated with This Genotype

Genotype
MGI:2449964

• Allelic Composition: Epb42^tm1Llp/Epb42^tm1Llp
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6J

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

hematopoietic system

increased spleen weight ( J:67412 )

• adult homozygotes show a 2-fold increase in spleen weight

anemia ( J:67412 )

• adult homozygotes are slightly anemic

abnormal erythrocyte morphology ( J:67412 )

• 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

decreased erythrocyte cell number ( J:67412 )

• adult homozygotes exhibit significantly reduced RBC counts relative to wild-type mice

• in contrast, white cell counts, platelet counts, and bleeding times remain unaffected

decreased hematocrit ( J:67412 )

• adult homozygotes exhibit significantly reduced hematocrits relative to wild-type mice

decreased hemoglobin content ( J:67412 )

• adult homozygotes display slightly reduced hemoglobin levels relative to wild-type mice

increased mean corpuscular hemoglobin concentration ( J:67412 )

• adult homozygotes display an elevated MCHC relative to wild-type mice

decreased mean corpuscular volume ( J:67412 )

• adult homozygotes exhibit a reduced MCV relative to wild-type mice

spherocytosis ( J:67412 )

• mutant RBCs display mild hereditary spherocytosis as a result of band 3 deficiency: lipid anchoring is impaired and unsupported lipids lost

reticulocytosis ( J:67412 )

• adult homozygotes exhibit a 2-fold increase in reticulocyte percentage

increased spleen iron level ( J:67412 )

• increased accumulation of iron in the spleen, indicating RBC damage

• no iron deposition is noted in the kidney, indicating absence of intravascular hemolysis

homeostasis/metabolism

dehydration ( J:67412 )

• mutant RBCs show altered cation content (increased K⁺/decreased Na⁺) resulting in dehydration

abnormal ion homeostasis ( J:67412 )

• 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 spleen iron level ( J:67412 )

• 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 spleen weight ( J:67412 )

• adult homozygotes show a 2-fold increase in spleen weight

increased spleen iron level ( J:67412 )

• increased accumulation of iron in the spleen, indicating RBC damage

• no iron deposition is noted in the kidney, indicating absence of intravascular hemolysis

growth/size/body

increased spleen weight ( J:67412 )

• adult homozygotes show a 2-fold increase in spleen weight

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
hereditary spherocytosis type 1		DOID:0110916	OMIM:182900	J:67412