Description

Strain Information

Former Names B6;129-Hbatm1(HBA)Tow Hbbtm2(HBG1,HBB*)Tow/J    (Changed: 24-JAN-11 ) Type Mutant Stock; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Species laboratory mouse Generation F?+F6 (12-MAR-13) Generation Definitions   Donating Investigator Dr. Tim Townes,   University of Alabama at Birmingham

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, these mice should 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, hα/hα::β^S/β^S, and hα/hα::β^A/β^A mice are viable and fertile. When carrying two copies of the β^S allele (i.e., hα/hα::β^S/β^S), mice develop a human sickle cell disease phenotype. Many rigid, elongated, sickle-shaped red blood cells (RBCs) are seen in blood smears from β^S/β^S mice. The spleens of β^S/β^S mice exhibit expansion of red pulp, pooling of sinusoidal erythrocytes, vasoocclusion, and a complete loss of lymphoid follicular structure. Focal areas of necrosis, hemosiderin deposition, and congestion of the vasculature with aggregates of sickled RBCs is evident in the liver. Erythroid progenitors are visible in the sinusoids and is indicative of severe anemia. Occlusion of blood vessels with sickled erythrocytes results in vascular, tubular, and glomerular changes in the kidneys. Reduced medullary blood flow causes tubular damage resulting in hyposthenuria. 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. The blood smears of corrected animals lack the characteristic erythrocytes of the β^S/β^S mice. Splenic structure and vasculature are normal, hepatic necrosis and erythrocyte aggregation are absent, and kidney function is restored. These mice may be useful in studying sickle cell disease.

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.

Control Information

	Control
	See control note:	Homozygous for Hbatm1(HBA)Tow, Homozygous for /Hbbtm3(HBG1,HBB)Tow (non-sickling from the colony)
	000664 C57BL/6J	(approximate)
Considerations for Choosing Controls

Related Strains

Strains carrying other alleles of HBB

003250	B6;129P2-Hbbtm2Unc/J
008314	C57BL/6-Tg(HBB-cre)12Kpe/J
003342	STOCK Hbatm1Paz Hbbtm1Tow Tg(HBA-HBBs)41Paz/J

View Strains carrying other alleles of HBB     (3 strains)

Strains carrying other alleles of HBG1

003342

STOCK Hbatm1Paz Hbbtm1Tow Tg(HBA-HBBs)41Paz/J

View Strains carrying other alleles of HBG1     (1 strain)

Strains carrying other alleles of Hba

002616	B6.129S7-Hbatm1Paz/J
001622	B6.Cg-Gpi1a Hbath-J
001175	B6.Cg-Hbap/J
000745	B6.SEC-Hbab/J
000191	B6.SM-Hbad/J
003342	STOCK Hbatm1Paz Hbbtm1Tow Tg(HBA-HBBs)41Paz/J
000802	WB.Cg-Hbath-J/J

View Strains carrying other alleles of Hba     (7 strains)

Strains carrying other alleles of Hbb

000409	B10.129P-H1b Hbbd Tyrc Ea7a/(5M)oSnJ
000418	B10.129P-H1b Tyrc Hbbd/(5M)nSnJ
000432	B10.C-H1b Hbbd Tyrc/(41N)SnJ
000562	B6(Cg)-Tubtub/J
002204	B6.129P2-Hbbtm1Unc/J
000383	B6.C-Tyrc H1b Hbbd/ByJ
002074	B6.Cg-Gpi1a Hbbd H1b/DehJ
000996	B6.D2-Hbbd3th/BrkJ
003250	B6;129P2-Hbbtm2Unc/J
000899	C.B6-Tyr+ Hbbs/J
000758	C57BL/6J-Hbbp Hrrh-7J/J
003342	STOCK Hbatm1Paz Hbbtm1Tow Tg(HBA-HBBs)41Paz/J
021452	STOCK Hbbd3th Tg(LCR-HBA1,LCR-HBB*)1Tow/J

View Strains carrying other alleles of Hbb     (13 strains)

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms provided by MGI

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

Sickle Cell Anemia

- Potential model based on gene homology relationships. Phenotypic similarity to the human disease has not been tested. Beta-Thalassemia   (HBB) Beta-Thalassemia, Dominant Inclusion Body Type   (HBB) Heinz Body Anemias   (HBB) Hemoglobin--Beta Locus; HBB   (HBB)

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI

      assigned by genotype

The following phenotype information may relate to a genetic background differing from this JAX^® Mice strain.

Hba^tm1(HBA)Tow/Hba^tm1(HBA)Tow Hbb^{tm2(HBG1,HBB*)Tow}/Hbb^{tm2(HBG1,HBB*)Tow}

        Background Not Specified

• hematopoietic system phenotype
• abnormal Kupffer cell morphology
  • abundant hemosiderin deposits   (MGI Ref ID J:134980)
• abnormal erythrocyte morphology   (MGI Ref ID J:134980)
• • anemia
    • slightly thalassemic   (MGI Ref ID J:137709)
  • anisocytosis   (MGI Ref ID J:134980)
  • decreased erythrocyte cell number   (MGI Ref ID J:134980)
  • decreased hematocrit   (MGI Ref ID J:134980)
  • decreased hemoglobin content   (MGI Ref ID J:134980)
  • poikilocytosis
    • many rigid elongated cells are seen in blood smears   (MGI Ref ID J:134980)
  • polychromatophilia   (MGI Ref ID J:134980)
• abnormal spleen white pulp morphology
  • complete loss of lymphoid follicular structure   (MGI Ref ID J:134980)
• enlarged spleen   (MGI Ref ID J:134980)
• extramedullary hematopoiesis
  • erythroid progenitors are present in the hepatic sinusoids   (MGI Ref ID J:134980)
• increased spleen red pulp amount
  • massive expansion of the red pulp   (MGI Ref ID J:134980)
• reticulocytosis   (MGI Ref ID J:134980)
• spleen vascular congestion
  • pooling of sinusoidal erythrocytes and vasoocclusion of splenic vessels   (MGI Ref ID J:134980)
• liver/biliary system phenotype
• abnormal liver morphology
  • pronounced congestion of intrahepatic vessels and aggregates of sickled red blood cells   (MGI Ref ID J:134980)
• • abnormal Kupffer cell morphology
    • abundant hemosiderin deposits   (MGI Ref ID J:134980)
  • focal hepatic necrosis   (MGI Ref ID J:134980)
  • increased liver iron level
    • abundant hemosiderin deposits in the Kupffer cells   (MGI Ref ID J:134980)
  • liver vascular congestion
    • pronounced congestion of intrahepatic vessels   (MGI Ref ID J:134980)
• renal/urinary system phenotype
• abnormal kidney corticomedullary boundary morphology
  • occlusion is most obvious at the corticomedullary junctions where dilated capillaries are easily detected   (MGI Ref ID J:134980)
• decreased urine osmolality   (MGI Ref ID J:134980)
• kidney vascular congestion
  • engorgement and occlusion of renal blood vessels   (MGI Ref ID J:134980)
  • occlusion is most obvious at the corticomedullary junctions where dilated capillaries are easily detected   (MGI Ref ID J:134980)
• cardiovascular system phenotype
• abnormal Kupffer cell morphology
  • abundant hemosiderin deposits   (MGI Ref ID J:134980)
• kidney vascular congestion
  • engorgement and occlusion of renal blood vessels   (MGI Ref ID J:134980)
  • occlusion is most obvious at the corticomedullary junctions where dilated capillaries are easily detected   (MGI Ref ID J:134980)
• liver vascular congestion
  • pronounced congestion of intrahepatic vessels   (MGI Ref ID J:134980)
• spleen vascular congestion
  • pooling of sinusoidal erythrocytes and vasoocclusion of splenic vessels   (MGI Ref ID J:134980)
• homeostasis/metabolism phenotype
• decreased urine osmolality   (MGI Ref ID J:134980)
• increased liver iron level
  • abundant hemosiderin deposits in the Kupffer cells   (MGI Ref ID J:134980)
• immune system phenotype
• abnormal Kupffer cell morphology
  • abundant hemosiderin deposits   (MGI Ref ID J:134980)
• abnormal spleen white pulp morphology
  • complete loss of lymphoid follicular structure   (MGI Ref ID J:134980)
• enlarged spleen   (MGI Ref ID J:134980)
• increased spleen red pulp amount
  • massive expansion of the red pulp   (MGI Ref ID J:134980)
• spleen vascular congestion
  • pooling of sinusoidal erythrocytes and vasoocclusion of splenic vessels   (MGI Ref ID J:134980)

View Research Applications

Research Applications

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

Developmental Biology Research
Internal/Organ Defects
      kidney
      kidney: vasculature
      liver

Hematological Research
Sickle Cell Anemia

Internal/Organ Research
Spleen Defects

HBB related

Hematological Research
Hemoglobin Defects

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		Hbatm1(HBA)Tow
Allele Name		targeted mutation 1, Timothy Townes
Allele Type		Targeted (knock-in)
Common Name(s)		HbA; Hbahalpha;
Expressed Gene		HBA, hemoglobin, alpha, human
Gene Symbol and Name		Hba, hemoglobin alpha chain complex
Chromosome		11
General Note		Mice homozygous for this allele and for Hbbtm2(HBG1,HBD,HBB*)Ryan allele Show Phenotypic Similarity to Human Syndrome: Beta Thalassemia Major and Cooley Anemia (J:148521) Mice homozygous for this allele and compound heterozygote for Hbbtm2(HBG1,HBD,HBB*)Ryan and Hbbtm3(HBG1,HBB)Tow alleles Show Phenotypic Similarity to Human Syndrome: Beta Thalassemia Minor (J:148521)
Molecular Note		The complex was replaced with human HBA. Details will be described elsewhere. [MGI Ref ID J:134980]
Allele Symbol		Hbbtm2(HBG1,HBB*)Tow
Allele Name		targeted mutation 2, Timothy Townes
Allele Type		Targeted (knock-in)
Common Name(s)		-1400-gamma-betaS; Hbbhbetas; Hbbtm2(HBB*)Tow;
Expressed Gene		HBB, hemoglobin, beta, human
Expressed Gene		HBG1, hemoglobin, gamma A, human
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, Hbatm1(HBA)Tow. Cre-mediated recombination removed the floxed hygro cassette. [MGI Ref ID J:134980] [MGI Ref ID J:44160]
Gene Symbol and Name		Hbb, hemoglobin beta chain complex
Chromosome		7
Allele Symbol		Hbbtm3(HBG1,HBB)Tow
Allele Name		targeted mutation 3, Timothy Townes
Allele Type		Targeted (knock-in)
Common Name(s)		-383 gamma-betaA; Hbbtm3(HBB)Tow;
Expressed Gene		HBB, hemoglobin, beta, human
Expressed Gene		HBG1, hemoglobin, gamma A, human
General Note		Mice heterozgyote for this and the Hbb allele, and homozygous for Hbatm1(HBA)Tow allele Show Phenotypic Similarity to Human Syndrome: Beta Thalassemia Minor (J:148521)
Molecular Note		In ES cells that were homozygous for Hbatm1(HBA)Tow and Hbbtm2(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. [MGI Ref ID J:134980]
Gene Symbol and Name		Hbb, hemoglobin beta chain complex
Chromosome		7

Genotyping

Genotyping Information

Genotyping Protocols

Hba^tm1(HBA)Tow, Melt Curve Analysis
Hba^tm1(HBA)Tow, Standard PCR
Hbb^{tm2(HBG1,HBB*)Tow}/Hbb^{tm3(HBG1,HBB)Tow}, Separated PCR

Hbb^{tm2(HBG1,HBB*)Tow}/Hbb^{tm3(HBG1,HBB)Tow}, Standard PCR

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

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):1183-8. [PubMed: 16638928]  [MGI Ref ID J:134980]

Additional References

Hba^tm1(HBA)Tow related

Chantrathammachart P; Mackman N; Sparkenbaugh E; Wang JG; Parise LV; Kirchhofer D; Key NS; Pawlinski R. 2012. Tissue factor promotes activation of coagulation and inflammation in a mouse model of sickle cell disease. Blood 120(3):636-46. [PubMed: 22661702]  [MGI Ref ID J:189104]

Ferreira A; Marguti I; Bechmann I; Jeney V; Chora A; Palha NR; Rebelo S; Henri A; Beuzard Y; Soares MP. 2011. Sickle hemoglobin confers tolerance to Plasmodium infection. Cell 145(3):398-409. [PubMed: 21529713]  [MGI Ref ID J:173413]

Hanna J; Wernig M; Markoulaki S; Sun CW; Meissner A; Cassady JP; Beard C; Brambrink T; Wu LC; Townes TM; Jaenisch R. 2007. Treatment of sickle cell anemia mouse model with iPS cells generated from autologous skin. Science 318(5858):1920-3. [PubMed: 18063756]  [MGI Ref ID J:130467]

Huo Y; McConnell SC; Ryan TM. 2009. Preclinical transfusion-dependent humanized mouse model of beta thalassemia major. Blood 113(19):4763-70. [PubMed: 19258591]  [MGI Ref ID J:148521]

Isbell TS; Sun CW; Wu LC; Teng X; Vitturi DA; Branch BG; Kevil CG; Peng N; Wyss JM; Ambalavanan N; Schwiebert L; Ren J; Pawlik KM; Renfrow MB; Patel RP; Townes TM. 2008. SNO-hemoglobin is not essential for red blood cell-dependent hypoxic vasodilation. Nat Med 14(7):773-7. [PubMed: 18516054]  [MGI Ref ID J:137709]

McConnell SC; Huo Y; Liu S; Ryan TM. 2011. Human globin knock-in mice complete fetal-to-adult hemoglobin switching in postnatal development. Mol Cell Biol 31(4):876-83. [PubMed: 21173165]  [MGI Ref ID J:170380]

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

Campbell AD; Cui S; Shi L; Urbonya R; Mathias A; Bradley K; Bonsu KO; Douglas RR; Halford B; Schmidt L; Harro D; Giacherio D; Tanimoto K; Tanabe O; Engel JD. 2011. Forced TR2/TR4 expression in sickle cell disease mice confers enhanced fetal hemoglobin synthesis and alleviated disease phenotypes. Proc Natl Acad Sci U S A 108(46):18808-13. [PubMed: 22042865]  [MGI Ref ID J:180224]

Chang J; Patton JT; Sarkar A; Ernst B; Magnani JL; Frenette PS. 2010. GMI-1070, a novel pan-selectin antagonist, reverses acute vascular occlusions in sickle cell mice. Blood 116(10):1779-86. [PubMed: 20508165]  [MGI Ref ID J:164535]

Chantrathammachart P; Mackman N; Sparkenbaugh E; Wang JG; Parise LV; Kirchhofer D; Key NS; Pawlinski R. 2012. Tissue factor promotes activation of coagulation and inflammation in a mouse model of sickle cell disease. Blood 120(3):636-46. [PubMed: 22661702]  [MGI Ref ID J:189104]

Hanna J; Wernig M; Markoulaki S; Sun CW; Meissner A; Cassady JP; Beard C; Brambrink T; Wu LC; Townes TM; Jaenisch R. 2007. Treatment of sickle cell anemia mouse model with iPS cells generated from autologous skin. Science 318(5858):1920-3. [PubMed: 18063756]  [MGI Ref ID J:130467]

Isbell TS; Sun CW; Wu LC; Teng X; Vitturi DA; Branch BG; Kevil CG; Peng N; Wyss JM; Ambalavanan N; Schwiebert L; Ren J; Pawlik KM; Renfrow MB; Patel RP; Townes TM. 2008. SNO-hemoglobin is not essential for red blood cell-dependent hypoxic vasodilation. Nat Med 14(7):773-7. [PubMed: 18516054]  [MGI Ref ID J:137709]

Kaul DK; Fabry ME; Suzuka SM; Zhang X. 2013. Antisickling fetal hemoglobin reduces hypoxia-inducible factor-1alpha expression in normoxic sickle mice: microvascular implications. Am J Physiol Heart Circ Physiol 304(1):H42-50. [PubMed: 23125209]  [MGI Ref ID J:192836]

Luo W; Campbell A; Wang H; Guo C; Bradley K; Wang J; Eitzman DT. 2012. P-selectin glycoprotein ligand-1 inhibition blocks increased leukocyte-endothelial interactions associated with sickle cell disease in mice. Blood 120(18):3862-4. [PubMed: 23118216]  [MGI Ref ID J:190985]

Meiler SE; Wade M; Kutlar F; Yerigenahally SD; Xue Y; Moutouh-de Parseval LA; Corral LG; Swerdlow PS; Kutlar A. 2011. Pomalidomide augments fetal hemoglobin production without the myelosuppressive effects of hydroxyurea in transgenic sickle cell mice. Blood 118(4):1109-12. [PubMed: 21536862]  [MGI Ref ID J:174901]

Ryan TM; Ciavatta DJ; Townes TM. 1997. Knockout-transgenic mouse model of sickle cell disease [see comments] Science 278(5339):873-6. [PubMed: 9346487]  [MGI Ref ID J:44160]

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

Chantrathammachart P; Mackman N; Sparkenbaugh E; Wang JG; Parise LV; Kirchhofer D; Key NS; Pawlinski R. 2012. Tissue factor promotes activation of coagulation and inflammation in a mouse model of sickle cell disease. Blood 120(3):636-46. [PubMed: 22661702]  [MGI Ref ID J:189104]

Hanna J; Wernig M; Markoulaki S; Sun CW; Meissner A; Cassady JP; Beard C; Brambrink T; Wu LC; Townes TM; Jaenisch R. 2007. Treatment of sickle cell anemia mouse model with iPS cells generated from autologous skin. Science 318(5858):1920-3. [PubMed: 18063756]  [MGI Ref ID J:130467]

Huo Y; McConnell SC; Ryan TM. 2009. Preclinical transfusion-dependent humanized mouse model of beta thalassemia major. Blood 113(19):4763-70. [PubMed: 19258591]  [MGI Ref ID J:148521]

Isbell TS; Sun CW; Wu LC; Teng X; Vitturi DA; Branch BG; Kevil CG; Peng N; Wyss JM; Ambalavanan N; Schwiebert L; Ren J; Pawlik KM; Renfrow MB; Patel RP; Townes TM. 2008. SNO-hemoglobin is not essential for red blood cell-dependent hypoxic vasodilation. Nat Med 14(7):773-7. [PubMed: 18516054]  [MGI Ref ID J:137709]

McConnell SC; Huo Y; Liu S; Ryan TM. 2011. Human globin knock-in mice complete fetal-to-adult hemoglobin switching in postnatal development. Mol Cell Biol 31(4):876-83. [PubMed: 21173165]  [MGI Ref ID J:170380]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           AX11

Colony Maintenance

Breeding & Husbandry

hα/hα::βA/βS :: Mice homozygous at the Hba locus for the hα mutation (Hbatm1(HBA)Tow) and harboring the -1400 γ-βS mutation (Hbbtm2(HBG1,HBB*)Tow) at the Hbb locus on one chromosome and the -383 γ-βA mutation (Hbbtm3(HBG1,HBB)Tow) at the Hbb locus on the other homologous chromosome are referred to as hα/hα::βA/βS. These mice do not harbor any wildtype allele at the Hbb locus. hα/hα::βS/βS :: Mice homozygous at the Hba locus for the hα mutation (Hbatm1(HBA)Tow) and homozygous at the Hbb locus for the -1400 γ-βS mutation (Hbbtm2(HBG1,HBB*)Tow) are referred to as hα/hα::βS/βS. These mice do not harbor any wildtype allele at the Hbb locus. hα/hα::βA/βA :: Mice homozygous at the Hba locus for the hα mutation (Hbatm1(HBA)Tow) and homozygous at the Hbb locus for the -383 γ-βA mutation (Hbbtm3(HBG1,HBB)Tow) are referred to as hα/hα::βA/βA. These mice do not harbor any wildtype allele at the Hbb locus. When maintaining a live colony, hα/hα::βA/βS females may be bred to hα/hα::βA/βS males, hα/hα::βA/βA males, or with hα/hα::βS/βS males. These mice should never be bred with wildtype mice or the humanized genes may be lost. Also, hα/hα::βS/βS females are poor mothers and should not be used for sustaining a live colony.

Diet Information

LabDiet® 5K52/5K67

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls

General Supply Notes

• Genomic DNA is available for this strain from the Mouse DNA Resource.

Control Information

	Control
	See control note:	Homozygous for Hbatm1(HBA)Tow, Homozygous for /Hbbtm3(HBG1,HBB)Tow (non-sickling from the colony)
	000664 C57BL/6J	(approximate)
Considerations for Choosing Controls
Control Pricing Information for Genetically Engineered Mutant Strains.

Payment Terms and Conditions

Terms are granted by individual review and stated on the customer invoice(s) and account statement. These transactions are payable in U.S. currency within the granted terms. Payment for services, products, shipping containers, and shipping costs that are rendered are expected within the payment terms indicated on the invoice or stated by contract. Invoices and account balances in arrears of stated terms may result in The Jackson Laboratory pursuing collection activities including but not limited to outside agencies and court filings.

See Terms of Use tab for General Terms and Conditions

The Jackson Laboratory's Genotype Promise

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.

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Ordering Information
JAX^® Mice
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JAX^® Services
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Tel: 1-800-422-6423 or 1-207-288-5845
Fax: 1-207-288-6150
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Terms of Use

Terms of Use

General Terms and Conditions

For Licensing and Use Restrictions view the link(s) below:
- Use of MICE by companies or for-profit entities requires a license prior to shipping.

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phone:	207-288-6470
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JAX^® Mice, Products & Services Conditions of Use

"MICE" means mouse strains, their progeny derived by inbreeding or crossbreeding, unmodified derivatives from mouse strains or their progeny supplied by The Jackson Laboratory ("JACKSON"). "PRODUCTS" means biological materials supplied by JACKSON, and their derivatives. "RECIPIENT" means each recipient of MICE, PRODUCTS, or services provided by JACKSON including each institution, its employees and other researchers under its control. MICE or PRODUCTS shall not be: (i) used for any purpose other than the internal research, (ii) sold or otherwise provided to any third party for any use, or (iii) provided to any agent or other third party to provide breeding or other services. Acceptance of MICE or PRODUCTS from JACKSON shall be deemed as agreement by RECIPIENT to these conditions, and departure from these conditions requires JACKSON's prior written authorization.

In case of dissatisfaction for a valid reason and claimed in writing by a purchaser within ninety (90) days of receipt of mice, products or services, JACKSON will, at its option, provide credit or replacement for the mice or product received or the services provided.

No Liability

In no event shall JACKSON, its trustees, directors, officers, employees, and affiliates be liable for any causes of action or damages, including any direct, indirect, special, or consequential damages, arising out of the provision of MICE, PRODUCTS or services, including economic damage or injury to property and lost profits, and including any damage arising from acts or negligence on the part of JACKSON, its agents or employees. Unless prohibited by law, in purchasing or receiving MICE, PRODUCTS or services from JACKSON, purchaser or recipient, or any party claiming by or through them, expressly releases and discharges JACKSON from all such causes of action or damages, and further agrees to defend and indemnify JACKSON from any costs or damages arising out of any third party claims.

MICE and PRODUCTS are to be used in a safe manner and in accordance with all applicable governmental rules and regulations.

The foregoing represents the General Terms and Conditions applicable to JACKSON’s MICE, PRODUCTS or services. In addition, special terms and conditions of sale of certain MICE, PRODUCTS or services may be set forth separately in JACKSON web pages, catalogs, price lists, contracts, and/or other documents, and these special terms and conditions shall also govern the sale of these MICE, PRODUCTS and services by JACKSON, and by its licensees and distributors.

Acceptance of delivery of MICE, PRODUCTS or services shall be deemed agreement to these terms and conditions. No purchase order or other document transmitted by purchaser or recipient that may modify the terms and conditions hereof, shall be in any way binding on JACKSON, and instead the terms and conditions set forth herein, including any special terms and conditions set forth separately, shall govern the sale of MICE, PRODUCTS or services by JACKSON.