Description

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Strain Information

Type Congenic; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Additional information on Congenic nomenclature. Species laboratory mouse Background Strain C57BL/6J Donor Strain 129P2 via E14TG2a ES cell line Generation N6   Donating Investigator Oliver Smithies,   University of North Carolina

Appearance
black
Related Genotype: a/a

Description
Homozygous mice die perinatally. Heterozygous mice show "characteristics typical of severe thalassemia" and are fertile.

Control Information

	Control
	Wild-type from the colony
	000664 C57BL/6J
Considerations for Choosing Controls

Related Strains

Strains carrying   Hbb-b1^tm1Unc allele

003253

B6;129P-Hbb-b1tm1Unc Hbb-b2tm1Unc/J

View Strains carrying   Hbb-b1^tm1Unc     (1 strain)

Strains carrying   Hbb-b2^tm1Unc allele

003253

B6;129P-Hbb-b1tm1Unc Hbb-b2tm1Unc/J

View Strains carrying   Hbb-b2^tm1Unc     (1 strain)

Additional Web Information

Congenic Nomenclature

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms

Hemoglobin--Beta Locus; HBB - Models with phenotypic similarity to human disease where etiologies are distinct.2

2 Human genes are associated with this disease. Orthologs of those genes do not appear in the mouse genotype(s).

View Mammalian Phenotype Terms

Mammalian Phenotype Terms

      assigned by genotype

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

Hbb-b1^tm1Unc/Hbb-b1⁺ Hbb-b2^tm1Unc/Hbb-b2⁺

        involves: 129P2/OlaHsd * C57BL/6J

• growth/size phenotype
• decreased body weight (MGI Ref ID J:30155)
  • F1 and F2 heterozygotes are significantly smaller
• hematopoietic system phenotype
• abnormal spleen morphology (MGI Ref ID J:88672)
  • hematopoietic stem cells from heterozygotes transfected with a large fragment of the human beta globin gene and injected back into the heterozygote restored normal spleen morphology
  • erythroid hyperplasia
  • megakaryocytes are present
  • iron particles are present in the macrophages in the centers of areas of erythropoiesis
• decreased spleen white pulp amount (MGI Ref ID J:30155)
  • the white pulp is almost completely replaced by hematopoietic tissue
• increased spleen weight (MGI Ref ID J:30155)
  • the spleen weight to body weight ratio is significantly greater in heterozygotes
• intermingled spleen red and white pulp (MGI Ref ID J:30155)
  • there is no clear distinction between the red and white pulp
• anemia (MGI Ref ID J:88672)
  • hematopoietic stem cells from heterozygotes transfected with a large fragment of the human beta globin gene and injected back into the heterozygote restored red blood cell counts to normal
  • at 7 weeks, mutants have a decreased red blood cell count with variation in the shape and inequality in the size (many microcytes and occasional polychromatic macrocytes) of the red blood cells
  • nucleated red blood cells are found
• decreased hematocrit (MGI Ref ID J:30155)
• decreased hemoglobin content (MGI Ref ID J:30155)
  • red blood cells are generally hypochromic
• increased bone marrow cell number (MGI Ref ID J:30155)
  • heterozygotes have increased bone marrow cellularity and increased numbers of megakaryocytes and erythroid precursors
• reticulocytosis (MGI Ref ID J:30155)
  • reticulocyte counts are increased 21-fold
• homeostasis/metabolism phenotype
• hemosiderosis (MGI Ref ID J:88672)
  • hematopoietic stem cells from heterozygotes transfected with a large fragment of the human beta globin gene and injected back into the heterozygote reduced abnormal iron accumulations
  • older (5-6 months) heterozygotes have iron accumulation in the proximal convoluted tubules of the kidney, and hepatocytes and Kupffer cells in the liver a sign of hemosiderosis
• increased circulating bilirubin level (MGI Ref ID J:30155)
  • serum concentrations of total and indirect bilirubin are elevated in mice 6 to 7 weeks old
• immune system phenotype
• abnormal spleen morphology (MGI Ref ID J:88672)
  • hematopoietic stem cells from heterozygotes transfected with a large fragment of the human beta globin gene and injected back into the heterozygote restored normal spleen morphology
  • erythroid hyperplasia
  • megakaryocytes are present
  • iron particles are present in the macrophages in the centers of areas of erythropoiesis
• decreased spleen white pulp amount (MGI Ref ID J:30155)
  • the white pulp is almost completely replaced by hematopoietic tissue
• increased spleen weight (MGI Ref ID J:30155)
  • the spleen weight to body weight ratio is significantly greater in heterozygotes
• intermingled spleen red and white pulp (MGI Ref ID J:30155)
  • there is no clear distinction between the red and white pulp
• limbs/digits/tail phenotype
• abnormal femur morphology (MGI Ref ID J:30155)
  • heterozygotes have a longer zone of proliferation and a shorter zone of osteogenesis
• skeleton phenotype
• abnormal femur morphology (MGI Ref ID J:30155)
  • heterozygotes have a longer zone of proliferation and a shorter zone of osteogenesis
• decreased cortical bone thickness (MGI Ref ID J:30155)
• skin/coat/nails phenotype
• pallor (MGI Ref ID J:30155)
  • heterozygotes are pale at birth

Hbb-b1^tm1Unc/Hbb-b1⁺ Hbb-b2^tm1Unc/Hbb-b2⁺

        involves: 129P2/OlaHsd * 129S6/SvEvTac * C57BL/6

• hematopoietic system phenotype
• decreased hematocrit (MGI Ref ID J:94421)

Hbb-b1^tm1Unc/Hbb-b1^tm1Unc Hbb-b2^tm1Unc/Hbb-b2^tm1Unc

        involves: 129P2/OlaHsd * C57BL/6J

• lethality-prenatal/perinatal
• perinatal lethality (MGI Ref ID J:30155)
  • all homozygous embryos are stillborn or die within 12 hours of birth

View Research Applications

Research Applications

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

Hbb-b1^tm1Unc related

Hematological Research
Hemoglobin Defects (beta^O-thalassemia)

Hbb-b2^tm1Unc related

Hemoglobin Defects (beta^O-thalassemia)

Genes & Alleles

Gene & Allele Information

Allele Symbol		Hbb-b1tm1Unc
Allele Name		targeted mutation 1, University of North Carolina
Allele Type		Targeted (knock-out)
Common Name(s)		Hbbth-3;
Strain of Origin		129P2/OlaHsd
ES Cell Line Name		E14TG2a
ES Cell Line Strain		129P2/OlaHsd
Gene Symbol and Name		Hbb-b1, hemoglobin, beta adult major chain
Chromosome		7
Gene Common Name(s)		AA409645; beta maj; beta major globin; expressed sequence AA409645;
Molecular Note		Hbb-b1 and Hbb-b2 were deleted using a two-step "plug and socket" method which leaves an hprt gene integrated in the genome. [MGI Ref ID J:20916]
Allele Symbol		Hbb-b2tm1Unc
Allele Name		targeted mutation 1, University of North Carolina
Allele Type		Targeted (knock-out)
Common Name(s)		Hbbth-3;
Strain of Origin		129P2/OlaHsd
ES Cell Line Name		E14TG2a
ES Cell Line Strain		129P2/OlaHsd
Gene Symbol and Name		Hbb-b2, hemoglobin, beta adult minor chain
Chromosome		7
Gene Common Name(s)		AI036344; beta min; beta minor globin; expressed sequence AI036344;
Molecular Note		Hbb-b1 and Hbb-b2 were deleted using a two-step "plug and socket" method which leaves an hprt gene integrated in the genome. [MGI Ref ID J:20916]

Genotyping

Genotyping Information

Genotyping Protocols

Generic HPRT_Alternative, SEP PCR, vers. 2
Hbb-b1^tm1Unc Hbb-b2^tm1Unc, SEP PCR, vers. 3
Human HPRT/KO2, SEP PCR, vers. 1
Human HPRT/KO2, SEP PCR, vers. 2

Helpful Links

Optimizing PCR Protocols

References

References

Selected Reference(s)

Yang B; Kirby S; Lewis J; Detloff PJ; Maeda N; Smithies O. 1995. A mouse model for beta 0-thalassemia. Proc Natl Acad Sci U S A 92(25):11608-12. [PubMed: 8524813]  [MGI Ref ID J:30155]

Additional References

Hbb-b1^tm1Unc related

Adamsky K; Weizer O; Amariglio N; Breda L; Harmelin A; Rivella S; Rachmilewitz E; Rechavi G. 2004. Decreased hepcidin mRNA expression in thalassemic mice. Br J Haematol 124(1):123-4. [PubMed: 14675418]  [MGI Ref ID J:88512]

Detloff PJ; Lewis J; John SW; Shehee WR; Langenbach R; Maeda N; Smithies O. 1994. Deletion and replacement of the mouse adult beta-globin genes by a plug and socket repeated targeting strategy. Mol Cell Biol 14(10):6936-43. [PubMed: 7935410]  [MGI Ref ID J:20916]

He Z; Russell JE. 2004. Antisickling effects of an endogenous human alpha-like globin. Nat Med 10(4):365-7. [PubMed: 15034572]  [MGI Ref ID J:131270]

Jamsai D; Zaibak F; Vadolas J; Voullaire L; Fowler KJ; Gazeas S; Peters H; Fucharoen S; Williamson R; Ioannou PA. 2006. A humanized BAC transgenic/knockout mouse model for HbE/beta-thalassemia. Genomics 88(3):309-15. [PubMed: 16631345]  [MGI Ref ID J:114910]

Kong Y; Zhou S; Kihm AJ; Katein AM; Yu X; Gell DA; Mackay JP; Adachi K; Foster-Brown L; Louden CS; Gow AJ; Weiss MJ. 2004. Loss of alpha-hemoglobin-stabilizing protein impairs erythropoiesis and exacerbates beta-thalassemia. J Clin Invest 114(10):1457-66. [PubMed: 15545996]  [MGI Ref ID J:94421]

Libani IV; Guy EC; Melchiori L; Schiro R; Ramos P; Breda L; Scholzen T; Chadburn A; Liu Y; Kernbach M; Baron-Luhr B; Porotto M; de Sousa M; Rachmilewitz EA; Hood JD; Cappellini MD; Giardina PJ; Grady RW; Gerdes J; Rivella S. 2008. Decreased differentiation of erythroid cells exacerbates ineffective erythropoiesis in beta-thalassemia. Blood 112(3):875-85. [PubMed: 18480424]  [MGI Ref ID J:138595]

May C; Rivella S; Chadburn A; Sadelain M. 2002. Successful treatment of murine beta-thalassemia intermedia by transfer of the human beta-globin gene. Blood 99(6):1902-8. [PubMed: 11877258]  [MGI Ref ID J:88672]

Romero JR; Suzuka SM; Nagel RL; Fabry ME. 2004. Expression of HbC and HbS, but not HbA, results in activation of K-Cl cotransport activity in transgenic mouse red cells. Blood 103(6):2384-90. [PubMed: 14615383]  [MGI Ref ID J:88563]

Russell JE; Liebhaber SA. 1998. Reversal of lethal alpha- and beta-thalassemias in mice by expression of human embryonic globins. Blood 92(9):3057-63. [PubMed: 9787139]  [MGI Ref ID J:114200]

Vadolas J; Nefedov M; Wardan H; Mansooriderakshan S; Voullaire L; Jamsai D; Williamson R; Ioannou PA. 2006. Humanized beta-thalassemia mouse model containing the common IVSI-110 splicing mutation. J Biol Chem 281(11):7399-405. [PubMed: 16421096]  [MGI Ref ID J:110556]

Vadolas J; Wardan H; Bosmans M; Zaibak F; Jamsai D; Voullaire L; Williamson R; Ioannou PA. 2005. Transgene copy number-dependent rescue of murine beta-globin knockout mice carrying a 183 kb human beta-globin BAC genomic fragment. Biochim Biophys Acta 1728(3):150-62. [PubMed: 15820143]  [MGI Ref ID J:124445]

Voon HP; Wardan H; Vadolas J. 2007. Co-inheritance of alpha- and beta-thalassaemia in mice ameliorates thalassaemic phenotype. Blood Cells Mol Dis 39(2):184-8. [PubMed: 17493845]  [MGI Ref ID J:141719]

Yu X; Kong Y; Dore LC; Abdulmalik O; Katein AM; Zhou S; Choi JK; Gell D; Mackay JP; Gow AJ; Weiss MJ. 2007. An erythroid chaperone that facilitates folding of alpha-globin subunits for hemoglobin synthesis. J Clin Invest 117(7):1856-65. [PubMed: 17607360]  [MGI Ref ID J:124209]

Hbb-b2^tm1Unc related

Adamsky K; Weizer O; Amariglio N; Breda L; Harmelin A; Rivella S; Rachmilewitz E; Rechavi G. 2004. Decreased hepcidin mRNA expression in thalassemic mice. Br J Haematol 124(1):123-4. [PubMed: 14675418]  [MGI Ref ID J:88512]

Detloff PJ; Lewis J; John SW; Shehee WR; Langenbach R; Maeda N; Smithies O. 1994. Deletion and replacement of the mouse adult beta-globin genes by a plug and socket repeated targeting strategy. Mol Cell Biol 14(10):6936-43. [PubMed: 7935410]  [MGI Ref ID J:20916]

He Z; Russell JE. 2004. Antisickling effects of an endogenous human alpha-like globin. Nat Med 10(4):365-7. [PubMed: 15034572]  [MGI Ref ID J:131270]

Kong Y; Zhou S; Kihm AJ; Katein AM; Yu X; Gell DA; Mackay JP; Adachi K; Foster-Brown L; Louden CS; Gow AJ; Weiss MJ. 2004. Loss of alpha-hemoglobin-stabilizing protein impairs erythropoiesis and exacerbates beta-thalassemia. J Clin Invest 114(10):1457-66. [PubMed: 15545996]  [MGI Ref ID J:94421]

Libani IV; Guy EC; Melchiori L; Schiro R; Ramos P; Breda L; Scholzen T; Chadburn A; Liu Y; Kernbach M; Baron-Luhr B; Porotto M; de Sousa M; Rachmilewitz EA; Hood JD; Cappellini MD; Giardina PJ; Grady RW; Gerdes J; Rivella S. 2008. Decreased differentiation of erythroid cells exacerbates ineffective erythropoiesis in beta-thalassemia. Blood 112(3):875-85. [PubMed: 18480424]  [MGI Ref ID J:138595]

May C; Rivella S; Chadburn A; Sadelain M. 2002. Successful treatment of murine beta-thalassemia intermedia by transfer of the human beta-globin gene. Blood 99(6):1902-8. [PubMed: 11877258]  [MGI Ref ID J:88672]

Nishino T; Cao H; Stamatoyannopoulos G; Emery DW. 2006. Effects of human gamma-globin in murine beta-thalassaemia. Br J Haematol 134(1):100-8. [PubMed: 16803575]  [MGI Ref ID J:110159]

Romero JR; Suzuka SM; Nagel RL; Fabry ME. 2004. Expression of HbC and HbS, but not HbA, results in activation of K-Cl cotransport activity in transgenic mouse red cells. Blood 103(6):2384-90. [PubMed: 14615383]  [MGI Ref ID J:88563]

Russell JE; Liebhaber SA. 1998. Reversal of lethal alpha- and beta-thalassemias in mice by expression of human embryonic globins. Blood 92(9):3057-63. [PubMed: 9787139]  [MGI Ref ID J:114200]

Vadolas J; Nefedov M; Wardan H; Mansooriderakshan S; Voullaire L; Jamsai D; Williamson R; Ioannou PA. 2006. Humanized beta-thalassemia mouse model containing the common IVSI-110 splicing mutation. J Biol Chem 281(11):7399-405. [PubMed: 16421096]  [MGI Ref ID J:110556]

Vadolas J; Wardan H; Bosmans M; Zaibak F; Jamsai D; Voullaire L; Williamson R; Ioannou PA. 2005. Transgene copy number-dependent rescue of murine beta-globin knockout mice carrying a 183 kb human beta-globin BAC genomic fragment. Biochim Biophys Acta 1728(3):150-62. [PubMed: 15820143]  [MGI Ref ID J:124445]

Voon HP; Wardan H; Vadolas J. 2007. Co-inheritance of alpha- and beta-thalassaemia in mice ameliorates thalassaemic phenotype. Blood Cells Mol Dis 39(2):184-8. [PubMed: 17493845]  [MGI Ref ID J:141719]

Yu X; Kong Y; Dore LC; Abdulmalik O; Katein AM; Zhou S; Choi JK; Gell D; Mackay JP; Gow AJ; Weiss MJ. 2007. An erythroid chaperone that facilitates folding of alpha-globin subunits for hemoglobin synthesis. J Clin Invest 117(7):1856-65. [PubMed: 17607360]  [MGI Ref ID J:124209]

Health & husbandry

Health & Colony Maintenance Information

Colony Maintenance

Diet Information	LabDiet® 5K52/5K67

Purchasing information

Pricing, Supply Level & Notes, Controls, General Terms & Conditions

Pricing

Supply Details

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes for further information.

Supply Notes

Cryorecovery - Standard. At least two mice that carry the mutation (if it is a mutant strain) will be provided. The total number of animals provided, their gender and genotype will vary. Please inquire if larger numbers of animals with specific genotypes and genders are needed. IMPORTANT NOTE: The genotypes of the animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire for possible genotypes for this specific strain. Animals typically ship within 13 to 16 weeks from your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will typically ship within 25 weeks. Cryorecovery to establish a Dedicated Supply for greater quantities of mice. One to two pairs will be recovered to establish a Dedicated Supply of mice. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 or 1-207-288-5845. This strain is included in the Induced Mutant Resource Colony collection. Genomic DNA is available for this strain from the Mouse DNA Resource.

Control Information

	Control
	Wild-type from the colony
	000664 C57BL/6J
Considerations for Choosing Controls
USA, Canada and Mexico - Control Pricing Information for Genetically Engineered Mutant Strains.
International - Control Pricing Information for Genetically Engineered Mutant Strains.

General Terms and Conditions

See Terms of Use

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 and Purchasing Information

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Contact Information
Orders & Technical Support
Tel: 800.422.6423 or 207.288.5845
Fax: 207.288.6150
Technical Support Email Form

Terms of Use

Terms of Use

General Terms and Conditions

Contact information

General inquiries

Contracts Administration

phone:	207-288-6470
fax:	207-288-6655

JAX^® Mice & Services Conditions of Use

“Each recipient institution, including its employees and other researchers under its control (RECIPIENT), of mice or services using mice from The Jackson Laboratory (TJL) agrees that such mice, descendants of those mice derived by inbreeding or crossbreeding, including unmodified derivatives of those mice or their descendants (“MICE”) shall not be: (i) used for any purpose other than the internal research of the RECIPIENT, (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 with respect to MICE. Acceptance of MICE from TJL shall be deemed agreement by RECIPIENT to these conditions, and departure from these conditions requires The Jackson Laboratory’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, The Jackson Laboratory will, at its option, provide credit or replacement for the MICE or product received or the services provided.

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In no event shall The Jackson Laboratory, 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 The Jackson Laboratory, its agents or employees. In purchasing or receiving MICE, products or services from The Jackson Laboratory, purchaser or recipient, or any party claiming by or through them, expressly releases and discharges The Jackson Laboratory from all such causes of action or damages, and further agrees to defend and indemnify The Jackson Laboratory from any costs or damages arising out of any third party claims.

MICE and biological materials 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 The Jackson Laboratory’s MICE, products and services. In addition, special terms and conditions of sale of certain MICE, products and services may be set forth separately in The Jackson Laboratory 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 The Jackson Laboratory, 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 The Jackson Laboratory, 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 services by The Jackson Laboratory.