Phenotypes associated with this allele

• Allele Symbol: Hbb^d3th
• Allele Name: beta-thalassemia
• Allele ID: MGI:1856047
• Summary: 8 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Hbb^d3th/Hbb^d3th	involves: C57BL/6 * DBA/2J	MGI:2450635
hm2	Hbb^d3th/Hbb^d3th	Not Specified	MGI:4412014
cx3	Hbb^d3th/Hbb^+ Tg(LCR-HBA1,LCR-HBB*)1Tow/0	involves: C57BL/6 * DBA/2J * SJL	MGI:5510724
cx4	Hbb^d3th/Hbb^+ Tg(LCR-HBA2,LCR-HBB*)1Cos/0	involves: C57BL/6J * CBA/J * DBA/2J	MGI:5509330
cx5	Hbb^d3th/Hbb^d3th Tg(LCR-HBA2,LCR-HBB)11Cos/0	involves: FVB/N	MGI:4412018
cx6	Hbb^d3th/Hbb^d3th Tg(HBB-AR-HBA2,-HBB*)58Rub/0 Tg(LCR-HBA2,LCR-HBB)11Cos/0	involves: FVB/N * Swiss Webster	MGI:4412015
cx7	Hbb^d3th/Hbb^+ Tg(HBB-AR-HBA2,-HBB*)58Rub/0 Tg(LCR-HBA2,LCR-HBB)11Cos/0	involves: FVB/N * Swiss Webster	MGI:4412016
cx8	Hbb^d3th/Hbb^d3th Tg(HBB-AR-HBA2,-HBB*)58Rub/0	involves: Swiss Webster	MGI:4412013

Genotype
MGI:2450635

hm1

• Allelic Composition: Hbb^d3th/Hbb^d3th
• Genetic Background: involves: C57BL/6 * DBA/2J

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

mortality/aging

postnatal lethality, incomplete penetrance ( J:7209 )

• although born at normal ratios, 37% die before weaning

• survival from weaning to 5 months of age is normal

hematopoietic system

abnormal erythrocyte morphology ( J:7209 )

low mean erythrocyte cell number ( J:7209 )

• RBC counts reduced to around 10.2 x 10⁶/mm³

decreased hematocrit ( J:7209 )

• around 37%

abnormal hemoglobin ( J:7209 )

• beta minor hemoglobin is elevated to about 24.6%

• reduced hemoglobin

• beta major hemoglobin is absent

abnormal hemoglobin content ( J:7209 )

• beta/alpha hemoglobin ratio is reduced

decreased mean corpuscular hemoglobin ( J:7209 )

decreased mean corpuscular volume ( J:7209 )

anisocytosis ( J:7209 )

• variable size of RBCs

anisopoikilocytosis ( J:7209 )

hyperchromasia ( J:7209 )

• increased numbers of nucleated RBCs

microcytosis ( J:7209 )

• large numbers of microcytes and cellular debris

poikilocytosis ( J:7209 )

reticulocytosis ( J:7209 )

reproductive system

decreased litter size ( J:7209 )

• reduced size of litters produced by females

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
beta thalassemia		DOID:12241	OMIM:613985	J:7209

Genotype
MGI:4412014

hm2

• Allelic Composition: Hbb^d3th/Hbb^d3th
• Genetic Background: Not Specified

hematopoietic system

decreased hematocrit ( J:136653 )

decreased mean corpuscular volume ( J:136653 )

reticulocytosis ( J:136653 )

Genotype
MGI:5510724

cx3

• 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

cx4

• 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:4412018

cx5

• Allelic Composition: Hbb^d3th/Hbb^d3th; Tg(LCR-HBA2,LCR-HBB)11Cos/0
• Genetic Background: involves: FVB/N

hematopoietic system

abnormal erythrocyte morphology ( J:94190 )

• under deoxygenated conditions, more than 39% of cells sickle in less than 50 seconds unlike wild-type cells

increased mean corpuscular hemoglobin ( J:94190 )

reticulocytosis ( J:94190 )

• in mice older than 30 days

Genotype
MGI:4412015

cx6

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

mortality/aging

premature death ( J:94190 )

• 20% of mice die by 5 months of age

postnatal lethality ( J:94190 )

• fewer than expected mice survive until P10

hematopoietic system

anemia ( J:94190 )

• mice exhibit neonatal anemia

abnormal erythrocyte morphology ( J:94190 )

• under deoxygenated conditions, more than 95% of cells sickle in less than 50 seconds and many exhibit profusion of spicules unlike wild-type cells

abnormal hemoglobin ( J:94190 )

• delay times for polymerization of hemoglobin are shorter than in Hbb^d3th/Hbb^d3th Tg(LCR-HBA2,LCR-HBB)11Cos mice

increased mean corpuscular hemoglobin ( J:94190 )

• compared with Hbb^d3th/Hbb^d3th Tg(LCR-HBA2,LCR-HBB)11Cos mice

reticulocytosis ( J:94190 )

abnormal spleen morphology ( J:94190 )

• mice exhibit spleen fibrosis unlike wild-type mice

spleen vascular congestion ( J:94190 )

• mice exhibit spleen congestion unlike wild-type mice

enlarged spleen ( J:94190 )

increased spleen red pulp amount ( J:94190 )

spleen fibrosis ( J:94190 )

homeostasis/metabolism

increased circulating alanine transaminase level ( J:94190 )

increased circulating aspartate transaminase level ( J:94190 )

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 )

cardiovascular system

abnormal kidney afferent arteriole morphology ( J:94190 )

• mice exhibit dilation of renal afferent vessels unlike wild-type mice

brain vascular congestion ( J:94190 )

• two younger mice exhibit congestion in the brain unlike wild-type mice

glomerular capillary congestion ( J:94190 )

• mice exhibit kidney glomerular congestion unlike wild-type mice

pulmonary vascular congestion ( J:94190 )

• mice exhibit lung congestion unlike wild-type mice

spleen vascular congestion ( J:94190 )

• mice exhibit spleen congestion unlike wild-type mice

pulmonary alveolar hemorrhage ( J:94190 )

• mice exhibit intra-alveolar hemorrhage unlike wild-type mice

liver/biliary system

abnormal liver morphology ( J:94190 )

• mice exhibit multifocal ischemic infarcts in the liver with dilation of the central vein and a preserved rim of viable cells around the central vein unlike wild-type mice

• older mice exhibit liver scarring and fibrosis with collapsed areas unlike wild-type mice

enlarged liver ( J:94190 )

liver fibrosis ( J:94190 )

• in older mice

nervous system

abnormal brain morphology ( J:94190 )

• two younger mice exhibit congestion in the brain, occasional red neurons, and rare pyknotic neurons unlike wild-type mice

brain vascular congestion ( J:94190 )

• two younger mice exhibit congestion in the brain unlike wild-type mice

abnormal neuron morphology ( J:94190 )

• mice exhibit red neurons unlike in wild-type mice

renal/urinary system

abnormal kidney afferent arteriole morphology ( J:94190 )

• mice exhibit dilation of renal afferent vessels unlike wild-type mice

glomerular capillary congestion ( J:94190 )

• mice exhibit kidney glomerular congestion unlike wild-type mice

enlarged kidney ( J:94190 )

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 fibrosis ( J:94190 )

• mice exhibit focal fibrosis in the medulla and the cortical-medullary junction unlike wild-type mice

• one mouse exhibits cortical fibrosis

respiratory system

pulmonary vascular congestion ( J:94190 )

• mice exhibit lung congestion unlike wild-type mice

pulmonary alveolar hemorrhage ( J:94190 )

• mice exhibit intra-alveolar hemorrhage unlike wild-type mice

pulmonary interstitial fibrosis ( J:94190 )

• in two older mice with some platelet thrombi

thick pulmonary interalveolar septum ( J:94190 )

• in two older mice

immune system

abnormal spleen morphology ( J:94190 )

• mice exhibit spleen fibrosis unlike wild-type mice

spleen vascular congestion ( J:94190 )

• mice exhibit spleen congestion unlike wild-type mice

enlarged spleen ( J:94190 )

increased spleen red pulp amount ( J:94190 )

spleen fibrosis ( J:94190 )

growth/size/body

enlarged kidney ( J:94190 )

enlarged liver ( J:94190 )

enlarged spleen ( J:94190 )

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

Genotype
MGI:4412016

cx7

• 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

Genotype
MGI:4412013

cx8

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

hematopoietic system

hematopoietic system phenotype ( J:136653 )

N • unlike Hbb^d3th homozygotes, mice do not exhibit anemia and exhibit normal mean corpuscular volume, hematocrit, and reticulocyte content under normal conditions

abnormal erythrocyte morphology ( J:136653 )

• 30% of red blood cells subjected to deoxygenation exhibit sickling unlike similarly treated wild-type or Hbb^d3th homozygous cells

abnormal mean corpuscular volume ( J:136653 )

• under hypoxic conditions, cell volume distribution is broader than in similarly treated wild-type cells

reticulocytosis ( J:94190 )