Phenotypes associated with this allele

• Allele Symbol: Hba^tm1(HBA)Tow
• Allele Name: targeted mutation 1, Timothy Townes
• Allele ID: MGI:3790755
• Summary: 10 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cx1	Hba^tm1(HBA)Tow/Hba^tm1(HBA)Tow Hbb^tm2(HBG1,HBB*)Tow/Hbb^tm2(HBG1,HBB*)Tow Slc12a4^Rbc10/Slc12a4^Rbc10	involves: 129 * BALB/c * C57BL/6J	MGI:5896636
cx2	Hba^tm1(HBA)Tow/Hba^tm1(HBA)Tow Hbb^tm2(HBG1,HBB*)Tow/Hbb^tm2(HBG1,HBB*)Tow Slc12a4^Rbc10/Slc12a4^+	involves: 129 * BALB/c * C57BL/6J	MGI:5896637
cx3	Hba^tm1(HBA)Tow/Hba^tm1(HBA)Tow Hbb^tm2(HBG1,HBB*)Tow/Hbb^tm3(HBG1,HBB)Tow Slc12a4^Rbc10/Slc12a4^Rbc10	involves: 129 * BALB/c * C57BL/6J	MGI:5896638
cx4	Hba^tm1(HBA)Tow/Hba^tm1(HBA)Tow Hbb^tm5(HBG1,HBB*)Tow/Hbb^tm5(HBG1,HBB*)Tow	Not Specified	MGI:3803750
cx5	Hba^tm1(HBA)Tow/Hba^tm1(HBA)Tow Hbb^tm3(HBG1,HBB)Tow/Hbb^tm3(HBG1,HBB)Tow	Not Specified	MGI:3803751
cx6	Hba^tm1(HBA)Tow/Hba^tm1(HBA)Tow Hbb^tm2(HBG1,HBB*)Tow/Hbb^tm2(HBG1,HBB*)Tow	Not Specified	MGI:3803707
cx7	Hba^tm1(HBA)Tow/Hba^tm1(HBA)Tow Hbb^tm2(HBG1,HBD,HBB*)Ryan/Hbb^tm2(HBG1,HBD,HBB*)Ryan	Not Specified	MGI:3846169
cx8	Hba^tm1(HBA)Tow/Hba^tm1(HBA)Tow Hbb^tm2(HBG1,HBD,HBB*)Ryan/Hbb^tm3(HBG1,HBB)Tow	Not Specified	MGI:3846168
cx9	Hba^tm1(HBA)Tow/Hba^tm1(HBA)Tow Hbb^tm2(HBG1,HBB*)Tow/Hbb^tm3(HBG1,HBB)Tow	Not Specified	MGI:3803708
cx10	Hba^tm1(HBA)Tow/Hba^tm1(HBA)Tow Hbb^tm4(HBB*)Tow/Hbb^tm4(HBB*)Tow	Not Specified	MGI:3803749

Genotype
MGI:5896636

cx1

• Allelic Composition: Hba^tm1(HBA)Tow/Hba^tm1(HBA)Tow; Hbb^{tm2(HBG1,HBB*)Tow}/Hbb^{tm2(HBG1,HBB*)Tow}; Slc12a4^Rbc10/Slc12a4^Rbc10
• Genetic Background: involves: 129 * BALB/c * C57BL/6J

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

mortality/aging

premature death ( J:227339 )

• only 1 mouse survived to 10 weeks of age

preweaning lethality, incomplete penetrance ( J:227339 )

• fewer than expected at 10 days of age

Genotype
MGI:5896637

cx2

• Allelic Composition: Hba^tm1(HBA)Tow/Hba^tm1(HBA)Tow; Hbb^{tm2(HBG1,HBB*)Tow}/Hbb^{tm2(HBG1,HBB*)Tow}; Slc12a4^Rbc10/Slc12a4⁺
• Genetic Background: involves: 129 * BALB/c * C57BL/6J

mortality/aging

premature death ( J:227339 )

• decreased survival compared to sickle mice wild-type for Slc12a4

hematopoietic system

enlarged spleen ( J:227339 )

• compared to sickle mice wild-type for Slc12a4

microcytic anemia ( J:227339 )

• increased anemia compared to mutant mice wild-type for Slc12a4

reticulocytosis ( J:227339 )

• increased compared to sickle mice wild-type for Slc12a4

abnormal erythrocyte physiology ( J:227339 )

• increase in ⁸⁶Rb efflux

• increased red cell density

liver/biliary system

liver inflammation ( J:227339 )

• marked lobular inflammation

abnormal liver morphology ( J:227339 )

• numerous sickle cells are seen in the sinusoids

hepatic necrosis ( J:227339 )

• centrilobular necrosis and congestion

cardiovascular system

abnormal pulmonary circulation ( J:227339 )

• increased intra-alveolar leakage of red cells

renal/urinary system

increased mesangial cell number ( J:227339 )

• mesangial proliferation

abnormal renal tubule morphology ( J:227339 )

• increase in the number of red cells in the tubules

respiratory system

abnormal pulmonary circulation ( J:227339 )

• increased intra-alveolar leakage of red cells

abnormal lung morphology ( J:227339 )

• increased interstitial congestion

immune system

enlarged spleen ( J:227339 )

• compared to sickle mice wild-type for Slc12a4

liver inflammation ( J:227339 )

• marked lobular inflammation

cellular

increased mesangial cell number ( J:227339 )

• mesangial proliferation

growth/size/body

enlarged spleen ( J:227339 )

• compared to sickle mice wild-type for Slc12a4

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
sickle cell anemia		DOID:10923		J:227339

Genotype
MGI:5896638

cx3

• Allelic Composition: Hba^tm1(HBA)Tow/Hba^tm1(HBA)Tow; Hbb^{tm2(HBG1,HBB*)Tow}/Hbb^{tm3(HBG1,HBB)Tow}; Slc12a4^Rbc10/Slc12a4^Rbc10
• Genetic Background: involves: 129 * BALB/c * C57BL/6J

hematopoietic system

microcytic anemia ( J:227339 )

• increased anemia compared to mutant mice wild-type for Slc12a4

Genotype
MGI:3803750

cx4

• Allelic Composition: Hba^tm1(HBA)Tow/Hba^tm1(HBA)Tow; Hbb^{tm5(HBG1,HBB*)Tow}/Hbb^{tm5(HBG1,HBB*)Tow}
• Genetic Background: Not Specified

hematopoietic system

anemia ( J:137709 )

• slightly thalassemic

abnormal erythrocyte physiology ( J:137709 )

• modest but significant increase in erythrocyte oxygen affinity

cardiovascular system

cardiovascular system phenotype ( J:137709 )

N • despite the absence of S-nitrosohemoglobin no signs of pulmonary hypertension or changes in hypoxic vasodilation response are seen

Genotype
MGI:3803751

cx5

• Allelic Composition: Hba^tm1(HBA)Tow/Hba^tm1(HBA)Tow; Hbb^{tm3(HBG1,HBB)Tow}/Hbb^{tm3(HBG1,HBB)Tow}
• Genetic Background: Not Specified

hematopoietic system

anemia ( J:137709 )

• slightly thalassemic

Genotype
MGI:3803707

cx6

• Allelic Composition: Hba^tm1(HBA)Tow/Hba^tm1(HBA)Tow; Hbb^{tm2(HBG1,HBB*)Tow}/Hbb^{tm2(HBG1,HBB*)Tow}
• Genetic Background: Not Specified

hematopoietic system

abnormal Kupffer cell morphology ( J:134980 )

• abundant hemosiderin deposits

spleen vascular congestion ( J:134980 )

• pooling of sinusoidal erythrocytes and vasoocclusion of splenic vessels

enlarged spleen ( J:134980 )

extramedullary hematopoiesis ( J:134980 )

• erythroid progenitors are present in the hepatic sinusoids

anemia ( J:137709 )

• slightly thalassemic

abnormal erythrocyte morphology ( J:134980 )

decreased erythrocyte cell number ( J:134980 )

decreased hematocrit ( J:134980 )

decreased hemoglobin content ( J:134980 )

anisocytosis ( J:134980 )

poikilocytosis ( J:134980 )

• many rigid elongated cells are seen in blood smears

polychromatophilia ( J:134980 )

reticulocytosis ( J:134980 )

increased spleen red pulp amount ( J:134980 )

• massive expansion of the red pulp

abnormal spleen white pulp morphology ( J:134980 )

• complete loss of lymphoid follicular structure

liver/biliary system

abnormal liver morphology ( J:134980 )

• pronounced congestion of intrahepatic vessels and aggregates of sickled red blood cells

abnormal Kupffer cell morphology ( J:134980 )

• abundant hemosiderin deposits

liver vascular congestion ( J:134980 )

• pronounced congestion of intrahepatic vessels

increased liver iron level ( J:134980 )

• abundant hemosiderin deposits in the Kupffer cells

focal hepatic necrosis ( J:134980 )

renal/urinary system

kidney vascular congestion ( J:134980 )

• engorgement and occlusion of renal blood vessels

• occlusion is most obvious at the corticomedullary junctions where dilated capillaries are easily detected

decreased urine osmolality ( J:134980 )

abnormal kidney corticomedullary boundary morphology ( J:134980 )

• occlusion is most obvious at the corticomedullary junctions where dilated capillaries are easily detected

cardiovascular system

kidney vascular congestion ( J:134980 )

• engorgement and occlusion of renal blood vessels

• occlusion is most obvious at the corticomedullary junctions where dilated capillaries are easily detected

abnormal Kupffer cell morphology ( J:134980 )

• abundant hemosiderin deposits

liver vascular congestion ( J:134980 )

• pronounced congestion of intrahepatic vessels

spleen vascular congestion ( J:134980 )

• pooling of sinusoidal erythrocytes and vasoocclusion of splenic vessels

homeostasis/metabolism

increased liver iron level ( J:134980 )

• abundant hemosiderin deposits in the Kupffer cells

decreased urine osmolality ( J:134980 )

immune system

abnormal Kupffer cell morphology ( J:134980 )

• abundant hemosiderin deposits

spleen vascular congestion ( J:134980 )

• pooling of sinusoidal erythrocytes and vasoocclusion of splenic vessels

enlarged spleen ( J:134980 )

increased spleen red pulp amount ( J:134980 )

• massive expansion of the red pulp

abnormal spleen white pulp morphology ( J:134980 )

• complete loss of lymphoid follicular structure

growth/size/body

enlarged spleen ( J:134980 )

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
sickle cell anemia		DOID:10923		J:134980

Genotype
MGI:3846169

cx7

• Allelic Composition: Hba^tm1(HBA)Tow/Hba^tm1(HBA)Tow; Hbb^{tm2(HBG1,HBD,HBB*)Ryan}/Hbb^{tm2(HBG1,HBD,HBB*)Ryan}
• Genetic Background: Not Specified

mortality/aging

premature death ( J:148521 )

• mice have a median survival of 14 days after birth

• 65% of mice die between 11 and 18 days of age

• some mice die as early as 1 day after birth and one mouse of 17 survived into adulthood

• lethality can be rescued by transfusion

hematopoietic system

spleen hyperplasia ( J:148521 )

• spleen as a percentage of bodyweight is 14-fold greater than controls

extramedullary hematopoiesis ( J:148521 )

• extramedullary hematopoiesis occurs in the spleen and liver

• large clusters of erythroblasts disrupt the architecture of the spleen and liver

anemia ( J:148521 )

• mice die of a lethal anemia

• anemia resembles beta thalassemia in humans

• anemia can be rescued by transfusion

hemolytic anemia ( J:148521 )

• blood smears showed numerous damaged RBCs

abnormal proerythroblast morphology ( J:148521 )

• proerythroblast and early erythroblast numbers are increased in the bone marrow and spleen

• there is a higher ratio of early erythroblasts to late erythroblasts in both tissues

• increased levels of apoptosis occur to early and late erythroblasts in the bone marrow

• increased levels of apoptosis occur to late erythroblasts in the spleen

low mean erythrocyte cell number ( J:148521 )

• red blood cell count is about 75% lower than controls

decreased hemoglobin content ( J:148521 )

• hemoglobin content is decreased by more than 4-fold

decreased mean corpuscular volume ( J:148521 )

• packed cell volume is decreased by almost two thirds

• red cell distribution width is greatly expanded

anisopoikilocytosis ( J:148521 )

• visible in blood smears

polychromatophilia ( J:148521 )

• nucleated cells with polychromatophilia are visible in blood smears

spherocytosis ( J:148521 )

• visible in blood smears

reticulocytosis ( J:148521 )

• percentage of reticulocytes in the blood is almost 72% compared to 3% in controls

intermingled spleen red and white pulp ( J:148521 )

• spleen architecture is disrupted by the presence of large numbers of erythroblasts

homeostasis/metabolism

increased circulating bilirubin level ( J:148521 )

• bilirubin levels are increased 150-fold in the blood

immune system

spleen hyperplasia ( J:148521 )

• spleen as a percentage of bodyweight is 14-fold greater than controls

intermingled spleen red and white pulp ( J:148521 )

• spleen architecture is disrupted by the presence of large numbers of erythroblasts

growth/size/body

spleen hyperplasia ( J:148521 )

• spleen as a percentage of bodyweight is 14-fold greater than controls

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
beta thalassemia		DOID:12241	OMIM:613985	J:148521

Genotype
MGI:3846168

cx8

• Allelic Composition: Hba^tm1(HBA)Tow/Hba^tm1(HBA)Tow; Hbb^{tm2(HBG1,HBD,HBB*)Ryan}/Hbb^{tm3(HBG1,HBB)Tow}
• Genetic Background: Not Specified

immune system

spleen hyperplasia ( J:148521 )

• spleen as a percentage of bodyweight is slightly increased

hematopoietic system

spleen hyperplasia ( J:148521 )

• spleen as a percentage of bodyweight is slightly increased

abnormal definitive hematopoiesis ( J:148521 )

• hemoglobin proteins are all of human origin

• at birth, blood contains 64% of human gamma globin chains and 36% human beta globin chains

• human beta-globin chain usage increases with age while gamma globin usage drops

• by 8 weeks of age beta-globin usage stabilizes at about 90% while delta and gamma chains make up about 5%

high mean erythrocyte cell number ( J:148521 )

• red blood cell count is about 10% higher than controls

decreased hemoglobin content ( J:148521 )

• hemoglobin content is decreased about 10%

decreased mean corpuscular volume ( J:148521 )

• packed cell volume is slightly decreased

reticulocytosis ( J:148521 )

• percentage of reticulocytes in the blood is increased

growth/size/body

spleen hyperplasia ( J:148521 )

• spleen as a percentage of bodyweight is slightly increased

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
beta thalassemia		DOID:12241	OMIM:613985	J:148521

Genotype
MGI:3803708

cx9

• Allelic Composition: Hba^tm1(HBA)Tow/Hba^tm1(HBA)Tow; Hbb^{tm2(HBG1,HBB*)Tow}/Hbb^{tm3(HBG1,HBB)Tow}
• Genetic Background: Not Specified

hematopoietic system

hematopoietic system phenotype ( J:134980 )

N • red blood cell morphology, hematological parameters, and spleen size and morphology are all similar to controls and no extramedullary hematopoiesis is detected unlike mice homozygous for Hbb^{tm2(HBG1,HBB*)Tow}

anemia ( J:137709 )

• slightly thalassemic

liver/biliary system

liver/biliary system phenotype ( J:134980 )

N • liver morphology is similar to controls

renal/urinary system

renal/urinary system phenotype ( J:134980 )

N • kidney morphology and physiology are similar to controls

Genotype
MGI:3803749

cx10

• Allelic Composition: Hba^tm1(HBA)Tow/Hba^tm1(HBA)Tow; Hbb^tm4(HBB*)Tow/Hbb^tm4(HBB*)Tow
• Genetic Background: Not Specified

hematopoietic system

anemia ( J:137709 )

• slightly thalassemic

abnormal erythrocyte physiology ( J:137709 )

• modest but significant increase in erythrocyte oxygen affinity

cardiovascular system

cardiovascular system phenotype ( J:137709 )

N • despite the absence of S-nitrosohemoglobin no signs of pulmonary hypertension or changes in hypoxic vasodilation response are seen