Phenotypes associated with this allele
Allelic
Composition |
Hbbd3th/Hbbd3th
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Genetic
Background |
involves: C57BL/6 * DBA/2J |
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Hbbd3th mutation
(4 available);
any
Hbb mutation
(47 available)
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mortality/aging
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• although born at normal ratios, 37% die before weaning
• survival from weaning to 5 months of age is normal
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hematopoietic system
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• RBC counts reduced to around 10.2 x 106/mm3
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• reduced hemoglobin
• beta major hemoglobin is absent
• beta minor hemoglobin is elevated to about 24.6%
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• beta/alpha hemoglobin ratio is reduced
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• increased numbers of nucleated RBCs
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• large numbers of microcytes and cellular debris
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reproductive system
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• reduced size of litters produced by females
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Hbbd3th mutation
(4 available);
any
Hbb mutation
(47 available)
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Hbbd3th mutation
(4 available);
any
Hbb mutation
(47 available)
Tg(LCR-HBA1,LCR-HBB*)1Tow mutation
(1 available)
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hematopoietic system
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• spleen is 2-4 times larger than control
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• decreased red blood cell counts
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• decreased hemoglobin concentration
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• 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
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• elevated reticulocyte counts
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immune system
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• spleen is 2-4 times larger than control
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growth/size/body
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• spleen is 2-4 times larger than control
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Hbbd3th mutation
(4 available);
any
Hbb mutation
(47 available)
Tg(LCR-HBA2,LCR-HBB*)1Cos mutation
(0 available)
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mortality/aging
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• mutants are extremely sensitive to hypoxia, with 9 of 10 mice dying within 90 min of exposure to 8% oxygen
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• progeny at weaning is less than expected; when hemizygous transgenic males are crossed with homozygous Hbbd3th 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
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hematopoietic system
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• large spleen in all adults
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• neonates are slightly more anemic than single Tg(LCR-HBA2,LCR-HBB*)1Cos, showing a 37% reduction in hematocrit
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• 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
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• slight decrease in in adults
• 37% reduction in neonates
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• polymerization of hemoglobin occurs faster than in single Tg(LCR-HBA2,LCR-HBB*)1Cos mice
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• increase in mean cell hemoglobin concentration
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• slight decrease in mean cell volume
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homeostasis/metabolism
immune system
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• large spleen in all adults
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growth/size/body
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• large spleen in all adults
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cellular
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• 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 Hbbd3th 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
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Hbbd3th mutation
(4 available);
any
Hbb mutation
(47 available)
Tg(LCR-HBA2,LCR-HBB)11Cos mutation
(1 available)
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hematopoietic system
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• under deoxygenated conditions, more than 39% of cells sickle in less than 50 seconds unlike wild-type cells
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• in mice older than 30 days
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Hbbd3th mutation
(4 available);
any
Hbb mutation
(47 available)
Tg(HBB-AR-HBA2,-HBB*)58Rub mutation
(1 available)
Tg(LCR-HBA2,LCR-HBB)11Cos mutation
(1 available)
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mortality/aging
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• 20% of mice die by 5 months of age
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• fewer than expected mice survive until P10
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hematopoietic system
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• mice exhibit neonatal anemia
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• under deoxygenated conditions, more than 95% of cells sickle in less than 50 seconds and many exhibit profusion of spicules unlike wild-type cells
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• delay times for polymerization of hemoglobin are shorter than in Hbbd3th/Hbbd3th Tg(LCR-HBA2,LCR-HBB)11Cos mice
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• compared with Hbbd3th/Hbbd3th Tg(LCR-HBA2,LCR-HBB)11Cos mice
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• mice exhibit spleen fibrosis unlike wild-type mice
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• mice exhibit spleen congestion unlike wild-type mice
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homeostasis/metabolism
cardiovascular system
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• mice exhibit dilation of renal afferent vessels unlike wild-type mice
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• two younger mice exhibit congestion in the brain unlike wild-type mice
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• mice exhibit kidney glomerular congestion unlike wild-type mice
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• mice exhibit lung congestion unlike wild-type mice
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• mice exhibit spleen congestion unlike wild-type mice
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• mice exhibit intra-alveolar hemorrhage unlike wild-type mice
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liver/biliary system
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• 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
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nervous system
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• two younger mice exhibit congestion in the brain, occasional red neurons, and rare pyknotic neurons unlike wild-type mice
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• two younger mice exhibit congestion in the brain unlike wild-type mice
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• mice exhibit red neurons unlike in wild-type mice
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renal/urinary system
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• mice exhibit dilation of renal afferent vessels unlike wild-type mice
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• mice exhibit kidney glomerular congestion unlike wild-type mice
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• after 7 hours of water deprivation, mice exhibit a reduced capacity to concentrate urine compared with similarly treated wild-type mice
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• mice exhibit focal fibrosis in the medulla and the cortical-medullary junction unlike wild-type mice
• one mouse exhibits cortical fibrosis
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respiratory system
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• mice exhibit lung congestion unlike wild-type mice
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• mice exhibit intra-alveolar hemorrhage unlike wild-type mice
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• in two older mice with some platelet thrombi
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immune system
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• mice exhibit spleen fibrosis unlike wild-type mice
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• mice exhibit spleen congestion unlike wild-type mice
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growth/size/body
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Hbbd3th mutation
(4 available);
any
Hbb mutation
(47 available)
Tg(HBB-AR-HBA2,-HBB*)58Rub mutation
(1 available)
Tg(LCR-HBA2,LCR-HBB)11Cos mutation
(1 available)
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homeostasis/metabolism
renal/urinary system
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• after 7 hours of water deprivation, mice exhibit a reduced capacity to concentrate urine compared with similarly treated wild-type mice
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hematopoietic system
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• mice exhibit neonatal anemia
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• under deoxygenated conditions, more than 17% of cells sickle in less than 50 seconds unlike wild-type cells
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Hbbd3th mutation
(4 available);
any
Hbb mutation
(47 available)
Tg(HBB-AR-HBA2,-HBB*)58Rub mutation
(1 available)
|
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hematopoietic system
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N |
• unlike Hbbd3th homozygotes, mice do not exhibit anemia and exhibit normal mean corpuscular volume, hematocrit, and reticulocyte content under normal conditions
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• 30% of red blood cells subjected to deoxygenation exhibit sickling unlike similarly treated wild-type or Hbbd3th homozygous cells
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• under hypoxic conditions, cell volume distribution is broader than in similarly treated wild-type cells
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Analysis Tools