Overview

Also Known As:hα/hα::β^A/β^S

These mice carry several human hemoglobin knock-in genes replacing the endogenous mouse genes and may be useful in studying sickle cell disease.

Donating Investigator

Paul Schmidt, Children's Hospital Boston

Genetic overview

Genetic Background	Generation
	?+F5 (2019-03-04 00:00:00)

Hbb^{tm2(HBG1,HBB)Tow}*

Allele Type	Gene Symbol	Gene Name
Targeted (Inserted expressed sequence, Humanized sequence)	Hbb	hemoglobin beta chain complex

Hbb^{tm3(HBG1,HBB)Tow}

Allele Type	Gene Symbol	Gene Name
Targeted (Inserted expressed sequence, Humanized sequence)	Hbb	hemoglobin beta chain complex

Allele Type	Gene Symbol	Gene Name
Targeted (Inserted expressed sequence, Humanized sequence)	Hba	hemoglobin alpha chain complex

Research Applications

Internal/Organ Research
Developmental Biology Research
Hematological Research

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Base Price

Starting at:

$255.00 Domestic price for female 4-week

510.00 Domestic price for breeder pair

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Details

Detailed Description

These mice may harbor several knockin mutations:
1) the Hba^tm1(HBA)Tow mutation (also called hα ; designed with the human hemoglobin α gene replacing the endogenous mouse α-globin),
as well as
2) the Hbb^{tm2(HBG1,HBB*)Tow} mutation (also called -1400 γ-β^S ; designed with the human hemoglobin gamma (^Aγ) gene and the human sickle hemoglobin beta (β^S) gene replacing the endogenous mouse major and minor β-globin),
and/or
3) the Hbb^{tm3(HBG1,HBB)Tow} mutation (also called -383 γ-β^A ; designed with the human hemoglobin gamma (^Aγ) gene and the human wildtype hemoglobin beta (β^A) gene replacing the endogenous mouse major and minor β-globin).

--Of note, mice homozygous for the β^S allele are not viable. These mice do not harbor any wildtype allele at the Hbb locus.

Mice homozygous at the Hba locus for the hα mutation and harboring the -1400 γ-β^S mutation at the Hbb locus on one chromosome and the -383 γ-β^A mutation at the Hbb locus on the other homologous chromosome are referred to as hα/hα::β^A/β^S.
Similarly, mice homozygous at the Hba locus for the hα mutation and homozygous at the Hbb locus for either the -1400 γ-β^S mutation or the -383 γ-β^A mutation are referred to as hα/hα::β^S/β^S or hα/hα::β^A/β^A, respectively.

The hα/hα::β^A/β^S and hα/hα::β^A/β^A mice are viable and fertile, hα/hα::β^S/β^S homozygous mice are not viable. In mice carrying at least one copy of the β^A allele (i.e., hα/hα::β^A/β^S and hα/hα::β^A/β^A), the sickle cell disease phenotype is corrected and the mice show no physical or behavioral abnormalities. These mice may be useful in studying sickle cell disease.

In an attempt to offer alleles on well-characterized or multiple genetic backgrounds, alleles are frequently moved to a genetic background different from that on which an allele was first characterized. It should be noted that the phenotype of these C57BL/6J-congenic mice could vary from that originally described on a B6;129 genetic background (Stock No. 013071). We may modify the strain description if necessary as published results become available.

Development

These mice harbor the hα (Hba^tm1(HBA)Tow) targeted mutation, the -1400 γ-β^S (Hbb^{tm2(HBG1,HBB*)Tow}) targeted mutation, and/or the -383 γ-β^A (Hbb^{tm3(HBG1,HBB)Tow}) targeted mutation. These mice should not harbor any wildtype allele at the Hbb locus.

The Hba^tm1(HBA)Tow targeted mutation (hα) was created by replacing the endogenous mouse α-globin gene with a human α-globin gene.

The Hbb^{tm2(HBG1,HBB*)Tow} targeted mutation (-1400 γ-β^S) was created by replacing the endogenous mouse major and minor β-globin genes with both the human ^Aγ gene (with 1400 bp of 5' flanking sequence) and the human β^S-globin gene (-1400 γ-β^S). The β^S gene contains an A to T mutation in the sixth codon of the human β-globin gene (resulting in a glutamic acid to valine conversion) that has been linked to sickle cell disease.

The Hbb^{tm3(HBG1,HBB)Tow} targeted mutation (-383 γ-β^A) was created by designing a targeting construct with the human hemoglobin gamma (^Aγ) gene with 383 bp of 5' flanking sequence, the human wildtype hemoglobin beta (β^A) gene with 815 bp of 5' flanking sequence, and a loxP-flanked phosphoglycerase/Hygromycin (PGK/Hygro) selection cassette.

The -383 γ-β^A targeting construct was electroporated into embryonic stem (ES) cells from knock-in sickle cell mice (homozygous for the hα targeted mutation and homozygous for the -1400 γ-β^S targeted mutation). The -383 γ-β^A construct contains 383 bp of 5' flanking sequence which is targeted to 1400 bp of 5' flanking sequence already present in the ES cells as part of the -1400 γ- β^S allele. Different recombination events in this flanking region produced two ES cell clones; clone 2 harbored the -383 γ-β^A replacement allele. This clone was then transiently transfected with a Cre expressing plasmid to delete the PGK/Hygro cassette, and then injected into recipient blastocysts. The resulting chimeric males were bred to females homozygous for hα and heterozygous for -1400 γ-β^S. Offspring with the sickle cell corrected genotypes (homozygous for hα and heterozygous at the Hbb locus (-383 γ-β^A/-1400 γ-β^S)) were obtained. These mice were maintained on a mixed C57BL/6;129 genetic background by breeding together for many generations prior to sending to The Jackson Laboratory Repository as Stock No. 013071.

Dr Paul Schmidt, from Boston Children's Hospital, purchased these mice and subsequently separated the three alleles in order to backcross the strain to C57BL/6J (Stock No. 00664). Each allele was bred to C57BL/6J for at least 10 generations before being bred back together in one strain.

Expression Data

Expressed Gene	HBG1, hemoglobin subunit gamma 1, human
Expressed Gene	HBB, hemoglobin subunit beta, human
Site of Expression
Expressed Gene	HBG1, hemoglobin subunit gamma 1, human
Expressed Gene	HBB, hemoglobin subunit beta, human
Site of Expression
Expressed Gene	HBA, hemoglobin, alpha, human
Site of Expression

Control Suggestions

Homozygous for Hba^tm1(HBA)Tow, Homozygous for /Hbb^{tm3(HBG1,HBB)Tow} (non-sickling from the colony)

Approximate Controls

000664 C57BL/6J

Additional Information

Considerations for Choosing Controls

Selected References

Wu LC; Sun CW; Ryan TM; Pawlik KM; Ren J; Townes TM. 2006. Correction of sickle cell disease by homologous recombination in embryonic stem cells. Blood 108(4):1183-8PubMed: 16638928 MGI: J:134980

View All References

Genetics

Hbb^{tm2(HBG1,HBB)Tow}*

Allele Symbol: Hbb^{tm2(HBG1,HBB)Tow}*

Allele Name	targeted mutation 2, Timothy Townes
Allele Type	Targeted (Inserted expressed sequence, Humanized sequence)
Allele Synonym(s)	-1400-gamma-beta^S; Hbb^hbetas; Hbb^tm2(HBB*)Tow; HbSS-Townes
Gene Symbol and Name	Hbb, hemoglobin beta chain complex
Gene Synonym(s)
Expressed Gene	HBG1, hemoglobin subunit gamma 1, human
Expressed Gene	HBB, hemoglobin subunit beta, human
Strain of Origin	Not Specified
Chromosome	7
Molecular Note	The major and minor beta chains were replaced with a construct made of a 5.66 kb fragment of the human gamma chain including 1400 bp of 5' flanking sequence and a 4.1 kb fragment of the sickle cell form of human HBB in ES cells already containing a replacement of Hba complex with human HBA, Hba^tm1(HBA)Tow. Cre-mediated recombination removed the floxed hygro cassette.

Hbb^{tm3(HBG1,HBB)Tow}

Allele Symbol: Hbb^{tm3(HBG1,HBB)Tow}

Allele Name	targeted mutation 3, Timothy Townes
Allele Type	Targeted (Inserted expressed sequence, Humanized sequence)
Allele Synonym(s)	-383 gamma-beta^A; Hbb^tm3(HBB)Tow
Gene Symbol and Name	Hbb, hemoglobin beta chain complex
Gene Synonym(s)
Expressed Gene	HBG1, hemoglobin subunit gamma 1, human
Expressed Gene	HBB, hemoglobin subunit beta, human
Strain of Origin	Not Specified
Chromosome	7
Molecular Note	In ES cells that were homozygous for Hba^tm1(HBA)Tow and Hbb^{tm2(HBG1,HBB*)Tow} the human gamma chain and beta chain containing the sickle cell mutation (an A to T transversion in the sixth codon) were replaced with the human gamma chain, beta chain (lacking the sickle cell mutation) and 383 bp of sequence flanking the gamma chain. Cre-mediated recombination removed the floxed hygro cassette.

Hba^tm1(HBA)Tow

Allele Symbol: Hba^tm1(HBA)Tow

Allele Name	targeted mutation 1, Timothy Townes
Allele Type	Targeted (Inserted expressed sequence, Humanized sequence)
Allele Synonym(s)	Hb^A; Hba^halpha
Gene Symbol and Name	Hba, hemoglobin alpha chain complex
Gene Synonym(s)
Expressed Gene	HBA, hemoglobin, alpha, human
Strain of Origin	Not Specified
Chromosome	11
Molecular Note	The complex was replaced with human HBA. Details will be described elsewhere.

Disease/Phenotype

Disease Terms

Research Areas By Phenotype

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

Internal/Organ Research
- Spleen Defects
Developmental Biology Research
- Internal/Organ Defects
  - kidney: vasculature
  - kidney
  - liver
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: Hba^tm1(HBA)Tow/Hba^tm1(HBA)Tow Hbb^{tm2(HBG1,HBB*)Tow}/Hbb^{tm3(HBG1,HBB)Tow}
Not Specified

hematopoietic system phenotype

anemia
- slightly thalassemic

mammalian phenotype

hematopoietic system phenotype
- Normal - red blood cell morphology, hematological parameters, and spleen size and morphology are all similar to controls and no extramedullary hematopoiesis is detected unlike mice homozygous for Hbb^{tm2(HBG1,HBB*)Tow}

liver/biliary system phenotype
- Normal - liver morphology is similar to controls

renal/urinary system phenotype
- Normal - kidney morphology and physiology are similar to controls

References

Wu LC; Sun CW; Ryan TM; Pawlik KM; Ren J; Townes TM. 2006. Correction of sickle cell disease by homologous recombination in embryonic stem cells. Blood 108(4):1183-8PubMed: 16638928 MGI: J:134980

Additional - Hba^tm1(HBA)Tow related

Additional - Hbb^{tm2(HBG1,HBB)Tow}* related

Additional - Hbb^{tm3(HBG1,HBB)Tow} related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- End Point Analysis:Hbb/Hbb-EP
- Probe:Hba Probe
- Genotyping resources and troubleshooting
Dietary Information
- New Diet as of March 2015: Lab Diet® 5K0Q (6% fat)
Breeding Considerations

hα/hα::β^A/β^S ::
Mice homozygous at the Hba locus for the hα mutation (Hba^tm1(HBA)Tow) and harboring the -1400 γ-β^S mutation (Hbb^{tm2(HBG1,HBB*)Tow}) at the Hbb locus on one chromosome and the -383 γ-β^A mutation (Hbb^{tm3(HBG1,HBB)Tow}) at the Hbb locus on the other homologous chromosome are referred to as hα/hα::β^A/β^S. These mice do not harbor any wildtype allele at the Hbb locus.
hα/hα::β^S/β^S ::
Mice homozygous at the Hba locus for the hα mutation (Hba^tm1(HBA)Tow) and homozygous at the Hbb locus for the -1400 γ-β^S mutation (Hbb^{tm2(HBG1,HBB*)Tow}) are referred to as hα/hα::β^S/β^S. These mice do not harbor any wildtype allele at the Hbb locus, and are not viable.
hα/hα::β^A/β^A ::
Mice homozygous at the Hba locus for the hα mutation (Hba^tm1(HBA)Tow) and homozygous at the Hbb locus for the -383 γ-β^A mutation (Hbb^{tm3(HBG1,HBB)Tow}) are referred to as hα/hα::β^A/β^A. These mice do not harbor any wildtype allele at the Hbb locus.
When maintaining a live colony, hα/hα::β^A/β^S females may be bred to hα/hα::β^A/β^S males or hα/hα::β^A/β^A males. These mice should never be bred with wildtype mice or the humanized genes may be lost.
- Additional Breeding and Husbandry Support
Mating System
- HOM(HBa):HET(HBb^A/HBb^S) females X HOM(HBa):HOM(HBb^A/Hbb^A), HOM(HBa):HOM(HBb^A/Hbb^S), or HOM(HBa):HOM(HBb^S/Hbb^S) males. NEVER mate w WT mice!
Citation
When using the hα/hα::β^A/β^S mouse strain in a publication, please cite the originating article(s) and include JAX stock #027265 in your Materials and Methods section.

Animal Health Reports

Facility Barrier Level Descriptions

AX18 (Maximum)

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The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project. We do not guarantee breeding performance and therefore suggest that investigators order more than one breeding pair to avoid delays in their research.

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Also Known As:hα/hα::βA/βS

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Expression Data

Control Suggestions

Approximate Controls

Additional Information

Selected References

Hbbtm2(HBG1,HBB*)Tow

Allele Symbol: Hbbtm2(HBG1,HBB*)Tow

Hbbtm3(HBG1,HBB)Tow

Allele Symbol: Hbbtm3(HBG1,HBB)Tow

Hbatm1(HBA)Tow

Allele Symbol: Hbatm1(HBA)Tow

Disease Terms

Research Areas By Phenotype

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

Mammalian Phenotype Terms by Genotype

Genotype: Hbatm1(HBA)Tow/Hbatm1(HBA)Tow Hbbtm2(HBG1,HBB*)Tow/Hbbtm3(HBG1,HBB)TowNot Specified

hematopoietic system phenotype

mammalian phenotype

References

Additional - Hbatm1(HBA)Tow related

Additional - Hbbtm2(HBG1,HBB*)Tow related

Additional - Hbbtm3(HBG1,HBB)Tow related

Genotyping Protocols

Dietary Information

Breeding Considerations

Mating System

Citation

Animal Health Reports

Live Mouse

Breeder Pair

Cryorecovery - Pricing

Payment Terms and Conditions

The Jackson Laboratory's Genotype Promise

Terms Of Use

Additional Use Restrictions Apply

Licensing Information

JAX® Mice, Products & Services Conditions of Use

No Warranty

Credit for PRODUCTS or SERVICES

Animal Care and Use for SERVICES

No Liability

Also Known As:hα/hα::β^A/β^S

Hbb^{tm2(HBG1,HBB)Tow}*

Allele Symbol: Hbb^{tm2(HBG1,HBB)Tow}*

Hbb^{tm3(HBG1,HBB)Tow}

Allele Symbol: Hbb^{tm3(HBG1,HBB)Tow}

Hba^tm1(HBA)Tow

Allele Symbol: Hba^tm1(HBA)Tow

Genotype: Hba^tm1(HBA)Tow/Hba^tm1(HBA)Tow Hbb^{tm2(HBG1,HBB*)Tow}/Hbb^{tm3(HBG1,HBB)Tow}
Not Specified

Additional - Hba^tm1(HBA)Tow related

Additional - Hbb^{tm2(HBG1,HBB)Tow}* related

Additional - Hbb^{tm3(HBG1,HBB)Tow} related