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 beta^S 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 Hbb^d3th mutation (also called β^major) containing a spontaneous deletion of endogenous Hbb gene.

Hb S mice were bred to Hbb^d3th 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.

Development

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 beta^S 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 beta^S, 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 Hbb^d3th mice containing a spontaneous deletion of the endogenous Hbb gene(β^major) 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.

Expression Data

Expressed Gene	HBA1, hemoglobin subunit alpha 1, human
Expressed Gene	HBB, hemoglobin subunit beta, human
Site of Expression

Control Suggestions

Wild-type from the colony
Noncarrier

Approximate Controls

Additional Information

Considerations for Choosing Controls

Selected References

Ryan TM; Townes TM; Reilly MP; Asakura T; Palmiter RD; Brinster RL; Behringer RR. 1990. Human sickle hemoglobin in transgenic mice. Science 247(4942):566-8PubMed: 2154033 MGI: J:127701

View All References

Genetics

Hbb^d3th

Allele Symbol: Hbb^d3th

Allele Name	beta-thalassemia
Allele Type	Spontaneous
Allele Synonym(s)	beta^major; beta^MDD; Hbb^d3(th); Hbb^th1; Hbb^th-1; Hbb^UNC
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.

Tg(LCR-HBA1,LCR-HBB*)1Tow

Allele Symbol: Tg(LCR-HBA1,LCR-HBB*)1Tow

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.

Disease/Phenotype

Disease Terms

Characteristics of this human disease are associated with transgenes and other mutation types in the mouse.

sickle cell anemia

Research Areas By Phenotype

This mouse can be used to support research in many areas including:

Internal/Organ Research
- Spleen Defects
Hematological Research
- Sickle Cell Anemia

Mammalian Phenotype Terms by Genotype

The following phenotype information is associated with a similar, but not exact match to this JAX^® Mice strain

Genotype: Hbb^d3th/Hbb⁺ Tg(LCR-HBA1,LCR-HBB)1Tow/0
involves: C57BL/6 DBA/2J * SJL

growth/size/body region phenotype

enlarged spleen
- spleen is 2-4 times larger than control

immune system phenotype

enlarged spleen
- spleen is 2-4 times larger than control

hematopoietic system phenotype

anemia
- mild anemia

anisopoikilocytosis
- 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

decreased erythrocyte cell number
- decreased red blood cell counts

decreased hematocrit

decreased hemoglobin content
- decreased hemoglobin concentration

echinocytosis

enlarged spleen
- spleen is 2-4 times larger than control

reticulocytosis
- elevated reticulocyte counts

References

Ryan TM; Townes TM; Reilly MP; Asakura T; Palmiter RD; Brinster RL; Behringer RR. 1990. Human sickle hemoglobin in transgenic mice. Science 247(4942):566-8PubMed: 2154033 MGI: J:127701

Additional - Hbb^d3th related

Additional - Tg(LCR-HBA1,LCR-HBB*)1Tow related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Separated PCR:Hbb Alternate5
- Standard PCR:Tg(HBA-HBBs)41Paz
- QPCR:Tg(HBA-HBBs)41Paz
- Genotyping resources and troubleshooting
Breeding Considerations

Hb S/β-thal mice heterozygous for the β^major deletion and carrying one transgene copy, may be bred to wildtype littermates, B6.D2-Hbb^d3th/BrkJ mice (Stock No. 000996), or C57BL/6J inbred mice (Stock No. 000664). Mice homozygous for the Hb S transgene are viable.
- Additional Breeding and Husbandry Support
Citation
When using the STOCK Hbb^d3th 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.

Animal Health Reports

Facility Barrier Level Descriptions

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

Pricing & Availability

Cryo Recovery

Domestic
International

Live Mouse

Age

Genotype

Price

weeks

Cryorecovery - Pricing

Service/Product	Description	Price
	Heterozygous or wildtype for Hbb<d3th>, Hemizygous or Non Carrier for Tg(LCR-HBA1,LCR-HBB*)1Tow

Related Products and Services

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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