Phenotypes associated with this allele

• Allele Symbol: Tg(LCR-HBA2,LCR-HBB*)1Cos
• Allele Name: transgene insertion 1, Frank Costantini
• Allele ID: MGI:5509327
• Summary: 2 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cx1	Hbb^d3th/Hbb^+ Tg(LCR-HBA2,LCR-HBB*)1Cos/0	involves: C57BL/6J * CBA/J * DBA/2J	MGI:5509330
tg2	Tg(LCR-HBA2,LCR-HBB*)1Cos/0	involves: C57BL/6J * CBA/J	MGI:5509328

Genotype
MGI:5509330

cx1

• 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

Genotype
MGI:5509328

tg2

• Allelic Composition: Tg(LCR-HBA2,LCR-HBB*)1Cos/0
• Genetic Background: involves: C57BL/6J * CBA/J

mortality/aging

postnatal lethality, incomplete penetrance ( J:94193 )

• frequency of offspring at weaning is 32% instead of the expected 50%

• frequency of mice at weaning is dependent on the genotype of the mother; frequency of hemizygotes is only 25% when the mother is non-transgenic and the father is hemizygous for the transgene, but 42% when the mother is hemizygous for the transgene and the father is non-transgenic

growth/size/body

decreased body size ( J:94193 )

• neonates are small in size

enlarged spleen ( J:94193 )

hematopoietic system

enlarged spleen ( J:94193 )

anemia ( J:94193 )

• neonates are anemic

abnormal erythrocyte morphology ( J:94193 )

• when fully oxygenated, a small percentage of red cells is elongated, resembling irreversibly sickled cells

• upon deoxygenation with nitrogen, almost all cells become irregular in shape, sickled, or with sharp elongations

• reoxygenation reverses these cell changes

decreased hematocrit ( J:94193 )

• hematocrit is decreased by 32% in neonates

increased mean corpuscular hemoglobin concentration ( J:94193 )

• mean cell hemoglobin concentration is increased

abnormal erythrocyte physiology ( J:94193 )

• oxygen affinity of erythroctyes is slightly lower than control erythrocytes

immune system

enlarged spleen ( J:94193 )

integument

pallor ( J:94193 )

• in neonates

cellular

maternal effect ( J:94193 )

• frequency of mice at weaning is dependent on the genotype of the mother and is dependent on oxygen affinity of maternal erythrocytes; frequency of hemizygotes is only 25% when the mother is non-transgenic and the father is hemizygous for the transgene, but 42% when the mother is hemizygous for the transgene and the father is non-transgenic