These mice may be useful in studying sickle cell disease.
Toshio Asakura, The Children's Hospital of Philadelphia
Genetic Background | Generation |
---|---|
|
Allele Type | Gene Symbol | Gene Name |
---|---|---|
Spontaneous | Hbb | hemoglobin beta chain complex |
Allele Type |
---|
Transgenic (Inserted expressed sequence, Humanized sequence) |
These mice harbor several mutations:
1) the Tg(LCRHBA1,LCRHBB)1Tow mutation (also called Hb S) designed with expression of the human hemoglobin beta chain complex (HBB) and human α1 globin (HBA1) being controlled independently by five upstream sites (HS I-V) of the human β-globin locus control regions (LCR). The HS I-V betaS transgene expresses a glutamic acid to valine mutation of the human hemoglobin beta chain complex (HBB) that has been linked to Sickle Cell Disease.
as well as
2) the Hbbd3th mutation (also called βmajor) containing a spontaneous deletion of endogenous Hbb gene.
Hb S mice were bred to Hbbd3th mice to increase expression of human β-globins in Hb S/β-thal mice. Hb S and Hb S/β-thal mice contain three and five times the level of endogenous mouse β-globin mRNA, respectively. They contain equivalent amounts of human α- and endogenous mouse α-globin mRNA. The donating investigator maintains the Hb S/β-thal mice by breeding mice heterozygous for the β-thal mutation and carrying one transgene copy. Mice homozygous for the β-thal mutation and homozygous for the transgene are viable.
Both groups exhibit decreased red blood cell counts and Hb concentrations. Reticulocyte counts are increased in Hb S/β-thal mice, indicating that they are mildly anemic. The spleens of Hb S/β-thal mice are two to four times larger than control spleens, as seen in children with sickle cell disease. Hypoxia (5% O2), causes the percentage of circulating sickled cells in the blood to increase, and leads to death from sickling-dependent pulmonary sequestration within 15 minutes.
Two transgenes were designed to each be controlled independently by five upstream sites (HS I-V) of the human β-globin locus control regions (LCR). The HS I-V betaS transgene expresses a glutamic acid to valine mutation of the human hemoglobin beta chain complex (HBB) that has been linked to sickle cell disease. The HS I-V alpha transgene expresses a human α1 globin (HBA1) gene. These constructs were coinjected into fertilized (C57BL/6 x SJL)F1 oocytes and insertion of the transgenes occured at a single locus. Founder mice, containing 5 copies of alpha and 7 copies of betaS, were obtained and bred to C57BL/6J mice. The resulting colony of Hb S mice was maintained by crossing transgenic mice to C57BL/6 mice.
Hb S mice were bred to Hbbd3th mice containing a spontaneous deletion of the endogenous Hbb gene(βmajor) which had been backcrossed to C57BL/6J. These Hb S/β-thal mice were maintained on a mixed background. Upon arrival at The Jackson Laboratory, these mice were bred to C57BL/6J mice (Stock No. 000664) for at least one generation to establish the colony.
Expressed Gene | HBA1, hemoglobin subunit alpha 1, human |
---|---|
Expressed Gene | HBB, hemoglobin subunit beta, human |
Site of Expression |
Allele Name | beta-thalassemia |
---|---|
Allele Type | Spontaneous |
Allele Synonym(s) | betamajor; betaMDD; Hbbd3(th); Hbbth1; Hbbth-1; HbbUNC |
Gene Symbol and Name | Hbb, hemoglobin beta chain complex |
Gene Synonym(s) | |
Strain of Origin | DBA/2J |
Chromosome | 7 |
Molecular Note | A 3.7 kb region, including the entire beta major globin gene and 2 kilobases of 5' flanking region, is deleted. A novel approximately 66 bp sequence ending in a poly(A) stretch was found to bridge the deletion. |
Allele Name | transgene insertion 1, Timothy Townes |
---|---|
Allele Type | Transgenic (Inserted expressed sequence, Humanized sequence) |
Allele Synonym(s) | Tg(LCR-HBA1,-HBB*)1Tow |
Gene Symbol and Name | Tg(LCR-HBA1,LCR-HBB*)1Tow, transgene insertion 1, Timothy Townes |
Gene Synonym(s) | |
Promoter | LCRB, locus control region, beta, human |
Expressed Gene | HBA1, hemoglobin subunit alpha 1, human |
Expressed Gene | HBB, hemoglobin subunit beta, human |
Strain of Origin | (C57BL/6 x SJL)F1 |
Chromosome | UN |
Molecular Note | Two transgenes were designed to each be controlled independently by five upstream sites (HS I-V) of the human beta-globin locus control regions (LCR). The HS I-V betaS transgene expresses a glutamic acid to valine mutation of the human hemoglobin beta chain complex (HBB) that has been linked to sickle cell disease. The HS I-V alpha transgene expresses a human alpha1 globin (HBA1) gene. Line 1 was generated. |
Hb S/β-thal mice heterozygous for the βmajor deletion and carrying one transgene copy, may be bred to wildtype littermates, B6.D2-Hbbd3th/BrkJ mice (Stock No. 000996), or C57BL/6J inbred mice (Stock No. 000664). Mice homozygous for the Hb S transgene are viable.
When using the STOCK Hbbd3th Tg(LCR-HBA1,LCR-HBB*)1Tow/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #021452 in your Materials and Methods section.
Facility Barrier Level Descriptions
Service/Product | Description | Price |
---|---|---|
Heterozygous or wildtype for Hbb<d3th>, Hemizygous or Non Carrier for Tg(LCR-HBA1,LCR-HBB*)1Tow |
Frozen Mouse Embryo | STOCK Hbb<d3th> Tg(LCR-HBA1 LCR-HBB*)1Tow/J | $2595.00 |
Frozen Mouse Embryo | STOCK Hbb<d3th> Tg(LCR-HBA1 LCR-HBB*)1Tow/J | $2595.00 |
Frozen Mouse Embryo | STOCK Hbb<d3th> Tg(LCR-HBA1 LCR-HBB*)1Tow/J | $3373.50 |
Frozen Mouse Embryo | STOCK Hbb<d3th> Tg(LCR-HBA1 LCR-HBB*)1Tow/J | $3373.50 |
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