Phenotypes associated with this allele

• Allele Symbol: Hbb⁺
• Allele Name: wild type
• Allele ID: MGI:3719107
• Summary: 8 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
ht1	Hbb^d4/Hbb^+	involves: 101/H	MGI:5050124
ht2	Hbb^tm2Unc/Hbb^+	involves: 129P2/OlaHsd * C57BL/6J	MGI:3835308
ht3	Hbb^tm1Tow/Hbb^+	involves: 129S2/SvPas * C57BL/6	MGI:3719108
ht4	Hbb^tm1.1(HBG1,HBB*)Ryan/Hbb^+	involves: C57BL/6J	MGI:3843172
cx5	Hba^tm1Paz/Hba^tm1Paz Hbb^tm1Tow/Hbb^+	involves: 129S2/SvPas * 129S7/SvEvBrd	MGI:5529821
cx6	Hbb^d3th/Hbb^+ Tg(LCR-HBA1,LCR-HBB*)1Tow/0	involves: C57BL/6 * DBA/2J * SJL	MGI:5510724
cx7	Hbb^d3th/Hbb^+ Tg(LCR-HBA2,LCR-HBB*)1Cos/0	involves: C57BL/6J * CBA/J * DBA/2J	MGI:5509330
cx8	Hbb^d3th/Hbb^+ Tg(HBB-AR-HBA2,-HBB*)58Rub/0 Tg(LCR-HBA2,LCR-HBB)11Cos/0	involves: FVB/N * Swiss Webster	MGI:4412016

Genotype
MGI:5050124

ht1

• Allelic Composition: Hbb^d4/Hbb⁺
• Genetic Background: involves: 101/H

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

hematopoietic system

increased erythrocyte cell number ( J:7972 )

• increase less marked compared with homozygotes

polycythemia ( J:7972 )

increased hematocrit ( J:7972 )

• increase less marked compared with homozygotes

increased mean corpuscular hemoglobin concentration ( J:7972 )

homeostasis/metabolism

increased blood oxygen capacity ( J:7972 )

• at 28.8 +/- 0.5 mm Hg, the mean pO₂ at 50% saturation is intermediate between that of a homozygous, 11.4 +/- 0.5 mm Hg, and a normal mouse, 46.2 +/- 2.0 mm Hg

Genotype
MGI:3835308

ht2

• Allelic Composition: Hbb^tm2Unc/Hbb⁺
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6J

hematopoietic system

enlarged spleen ( J:64295 )

• 2% of body weight compared to 0.2% in wild-type mice

extramedullary hematopoiesis ( J:64295 )

• in the liver

abnormal erythrocyte morphology ( J:64295 )

decreased erythrocyte cell number ( J:64295 )

decreased hematocrit ( J:64295 )

increased hemoglobin concentration distribution width ( J:64295 )

decreased hemoglobin content ( J:64295 )

increased mean corpuscular hemoglobin concentration ( J:64295 )

decreased mean corpuscular volume ( J:64295 )

anisocytosis ( J:64295 )

poikilocytosis ( J:64295 )

increased spleen iron level ( J:64295 )

• by 5 months of age

liver/biliary system

increased liver iron level ( J:64295 )

• by 5 months of age

renal/urinary system

increased kidney iron level ( J:64295 )

• greater than in wild-type mice by 5 months of age

homeostasis/metabolism

increased spleen iron level ( J:64295 )

• by 5 months of age

increased kidney iron level ( J:64295 )

• greater than in wild-type mice by 5 months of age

increased liver iron level ( J:64295 )

• by 5 months of age

immune system

enlarged spleen ( J:64295 )

• 2% of body weight compared to 0.2% in wild-type mice

increased spleen iron level ( J:64295 )

• by 5 months of age

growth/size/body

enlarged spleen ( J:64295 )

• 2% of body weight compared to 0.2% in wild-type mice

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
beta thalassemia		DOID:12241	OMIM:613985	J:64295

Genotype
MGI:3719108

ht3

• Allelic Composition: Hbb^tm1Tow/Hbb⁺
• Genetic Background: involves: 129S2/SvPas * C57BL/6

hematopoietic system

enlarged spleen ( J:29087 )

• spleens are dramatically enlarged

increased spleen weight ( J:29087 )

• spleens weight is increased to 800mg compared to 80mg in wild-type mice

anemia ( J:29087 )

increased bone marrow cell number ( J:29087 )

decreased hemoglobin content ( J:29087 )

• hemoglobin levels are lower than in wild-type mice (7.1+/-0.5 g/dl compared to 14.9+/-0.7 g/dl

anisopoikilocytosis ( J:29087 )

reticulocytosis ( J:29087 )

immune system

enlarged spleen ( J:29087 )

• spleens are dramatically enlarged

increased spleen weight ( J:29087 )

• spleens weight is increased to 800mg compared to 80mg in wild-type mice

growth/size/body

enlarged spleen ( J:29087 )

• spleens are dramatically enlarged

increased spleen weight ( J:29087 )

• spleens weight is increased to 800mg compared to 80mg in wild-type mice

Genotype
MGI:3843172

ht4

• Allelic Composition: Hbb^{tm1.1(HBG1,HBB*)Ryan}/Hbb⁺
• Genetic Background: involves: C57BL/6J

Hbb^{tm1.1(HBG1,HBB*)Ryan}/Hbb⁺ mice have a severe Beta Thalassemic phenotype

hematopoietic system

extramedullary hematopoiesis ( J:147906 )

microcytic anemia ( J:147906 )

• seen in adults

• results in the release of nascent macrocytic red blood cells and reticulocytes into circulation

increased erythroid progenitor cell number ( J:147906 )

• enlarged femoral bone marrow cavities are filled with erythroid progenitors

decreased erythrocyte cell number ( J:147906 )

increased hemoglobin concentration distribution width ( J:147906 )

• the red cell distribution width is double that of controls

decreased mean corpuscular hemoglobin ( J:147906 )

decreased mean corpuscular hemoglobin concentration ( J:147906 )

decreased mean corpuscular volume ( J:147906 )

anisopoikilocytosis ( J:147906 )

• numerous targeted and hypochromic red cells are present

reticulocytosis ( J:147906 )

• about a 9 fold increase in reticulocyte counts

abnormal spleen morphology ( J:147906 )

enlarged spleen ( J:147906 )

• 6 fold increase in size, as a percentage of body weight

increased spleen iron level ( J:147906 )

• destruction of erythroid cells leads to increased deposition of iron in the spleen

increased spleen red pulp amount ( J:147906 )

intermingled spleen red and white pulp ( J:147906 )

• splenic architecture is disrupted by the expansion of the red pulp

skeleton

abnormal bone marrow cavity morphology ( J:147906 )

• enlarged femoral bone marrow cavity

homeostasis/metabolism

abnormal iron level ( J:147906 )

• destruction of erythroid cells leads to increased deposition of iron in the bone marrow

increased spleen iron level ( J:147906 )

• destruction of erythroid cells leads to increased deposition of iron in the spleen

increased liver iron level ( J:147906 )

• destruction of erythroid cells leads to increased deposition of iron in the liver

liver/biliary system

increased liver iron level ( J:147906 )

• destruction of erythroid cells leads to increased deposition of iron in the liver

immune system

abnormal spleen morphology ( J:147906 )

enlarged spleen ( J:147906 )

• 6 fold increase in size, as a percentage of body weight

increased spleen iron level ( J:147906 )

• destruction of erythroid cells leads to increased deposition of iron in the spleen

increased spleen red pulp amount ( J:147906 )

intermingled spleen red and white pulp ( J:147906 )

• splenic architecture is disrupted by the expansion of the red pulp

growth/size/body

enlarged spleen ( J:147906 )

• 6 fold increase in size, as a percentage of body weight

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
beta thalassemia		DOID:12241	OMIM:613985	J:147906

Genotype
MGI:5529821

cx5

• Allelic Composition: Hba^tm1Paz/Hba^tm1Paz; Hbb^tm1Tow/Hbb⁺
• Genetic Background: involves: 129S2/SvPas * 129S7/SvEvBrd

hematopoietic system

hematopoietic system phenotype ( J:204029 )

N • mice exhibit normal erythroid development

Genotype
MGI:5510724

cx6

• Allelic Composition: Hbb^d3th/Hbb⁺; Tg(LCR-HBA1,LCR-HBB*)1Tow/0
• Genetic Background: involves: C57BL/6 * DBA/2J * SJL

hematopoietic system

enlarged spleen ( J:127701 )

• spleen is 2-4 times larger than control

anemia ( J:127701 )

• mild anemia

decreased erythrocyte cell number ( J:127701 )

• decreased red blood cell counts

decreased hematocrit ( J:127701 )

decreased hemoglobin content ( J:127701 )

• decreased hemoglobin concentration

anisopoikilocytosis ( J:127701 )

• 90% of deoxygenated cells exhibit sickled shapes as compared to 1% of the transgene only mice

• sickled erythrocytes have projections or spicules similar to human sickled cells

echinocytosis ( J:127701 )

reticulocytosis ( J:127701 )

• elevated reticulocyte counts

immune system

enlarged spleen ( J:127701 )

• spleen is 2-4 times larger than control

growth/size/body

enlarged spleen ( J:127701 )

• spleen is 2-4 times larger than control

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
sickle cell anemia		DOID:10923		J:127701

Genotype
MGI:5509330

cx7

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

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:4412016

cx8

• Allelic Composition: Hbb^d3th/Hbb⁺; Tg(HBB-AR-HBA2,-HBB*)58Rub/0; Tg(LCR-HBA2,LCR-HBB)11Cos/0
• Genetic Background: involves: FVB/N * Swiss Webster

homeostasis/metabolism

increased circulating alanine transaminase level ( J:94190 )

• intermediately

increased circulating aspartate transaminase level ( J:94190 )

• intermediately

abnormal urine homeostasis ( J:94190 )

• after 7 hours of water deprivation, mice exhibit a reduced capacity to concentrate urine compared with similarly treated wild-type mice

decreased urine osmolality ( J:94190 )

renal/urinary system

abnormal urine homeostasis ( J:94190 )

• after 7 hours of water deprivation, mice exhibit a reduced capacity to concentrate urine compared with similarly treated wild-type mice

decreased urine osmolality ( J:94190 )

hematopoietic system

anemia ( J:94190 )

• mice exhibit neonatal anemia

abnormal erythrocyte morphology ( J:94190 )

• under deoxygenated conditions, more than 17% of cells sickle in less than 50 seconds unlike wild-type cells

reticulocytosis ( J:94190 )

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
sickle cell anemia		DOID:10923		J:94190