Phenotypes Associated with This Genotype

Genotype
MGI:5509330

• Allelic Composition: Hbb^d3th/Hbb⁺; Tg(LCR-HBA2,LCR-HBB*)1Cos/0
• Genetic Background: involves: C57BL/6J * CBA/J * DBA/2J

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

mortality/aging

increased susceptibility to induced morbidity/mortality ( J:94193 )

• mutants are extremely sensitive to hypoxia, with 9 of 10 mice dying within 90 min of exposure to 8% oxygen

postnatal lethality, incomplete penetrance ( J:94193 )

• progeny at weaning is less than expected; when hemizygous transgenic males are crossed with homozygous Hbb^d3th females, frequency of progeny at weaning is only 9%, while for the reciprocal cross, it is 30% instead of the expected 50% for either cross

hematopoietic system

enlarged spleen ( J:94193 )

• large spleen in all adults

anemia ( J:94193 )

• neonates are slightly more anemic than single Tg(LCR-HBA2,LCR-HBB*)1Cos, showing a 37% reduction in hematocrit

abnormal erythrocyte morphology ( J:94193 )

• erythrocytes show abnormal size and shape, with 5-15% of erythrocytes being small and elongated, resembling irreversible sickle cells

• erythrocyte show heterogenous cell density, with a fraction of cells displaying high density

• most erythrocytes become sickled upon deoxygenation

decreased hematocrit ( J:94193 )

• slight decrease in in adults

• 37% reduction in neonates

abnormal hemoglobin ( J:94193 )

• polymerization of hemoglobin occurs faster than in single Tg(LCR-HBA2,LCR-HBB*)1Cos mice

increased mean corpuscular hemoglobin concentration ( J:94193 )

• increase in mean cell hemoglobin concentration

decreased mean corpuscular volume ( J:94193 )

• slight decrease in mean cell volume

reticulocytosis ( J:94193 )

homeostasis/metabolism

abnormal gas homeostasis ( J:94193 )

• mutants are extremely sensitive to hypoxia, with 9 of 10 mice dying within 90 min of exposure to 8% oxygen

immune system

enlarged spleen ( J:94193 )

• large spleen in all adults

growth/size/body

enlarged spleen ( J:94193 )

• large spleen in all adults

cellular

maternal effect ( J:94193 )

• frequency of mice at weaning is dependent on the genotype of the mother and is partly dependent on oxygen affinity of maternal erythrocytes; when hemizygous transgenic males are crossed with homozygous Hbb^d3th females, frequency of progeny at weaning is only 9%, while for the reciprocal cross, it is 30% instead of the expected 50% for either cross

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
sickle cell anemia		DOID:10923		J:94193