Phenotypes associated with this allele

• Allele Symbol: Hbb^{tm2(HBG1,HBD,HBB*)Ryan}
• Allele Name: targeted mutation 2, Thomas M Ryan
• Allele ID: MGI:3846101
• Summary: 2 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cx1	Hba^tm1(HBA)Tow/Hba^tm1(HBA)Tow Hbb^tm2(HBG1,HBD,HBB*)Ryan/Hbb^tm3(HBG1,HBB)Tow	Not Specified	MGI:3846168
cx2	Hba^tm1(HBA)Tow/Hba^tm1(HBA)Tow Hbb^tm2(HBG1,HBD,HBB*)Ryan/Hbb^tm2(HBG1,HBD,HBB*)Ryan	Not Specified	MGI:3846169

Genotype
MGI:3846168

cx1

• 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

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

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:3846169

cx2

• 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