Description

Strain Information

Former Names B6.129S7-Hba-a1tm1Paz Hba-a2tm1Paz/J    (Changed: 07-AUG-08 ) Type Congenic; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered Mutant Mice. Species laboratory mouse Background Strain C57BL/6 Donor Strain 129S7 via AB1 ES cell line (+Hprt-bm2) Generation B6N8   Donating Investigator Chris Paszty,   Amgen, Inc.

Appearance
black
Related Genotype: a/a

Description
Mice homozygous for this mutation die in utero. The apparent cause of death is severe anemia as no alpha-globin polypeptide is found in these animals.

Control Information

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

Related Strains

Strains carrying   Hba^tm1Paz allele

003342

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

View Strains carrying   Hba^tm1Paz     (1 strain)

Strains carrying other alleles of Hba

001622	B6.CAST-Gpi1a.Cg-Hbath-J
000802	WB.Cg-Hbath-J/J

View Strains carrying other alleles of Hba     (2 strains)

Additional Web Information

Congenic Nomenclature

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms

	Hemoglobin--Alpha Locus 1; HBA1 -
	Hydrops Fetalis, Idiopathic -

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.

Hba^tm1Paz/Hba^tm1Paz

        involves: 129S7/SvEvBrd

• lethality-prenatal/perinatal
• lethality throughout fetal growth and development (MGI Ref ID J:28392)
  • death between E14.5 and E16.5
• growth/size phenotype
• reduced fetal size (MGI Ref ID J:28392)
  • noticeably smaller than littermates at E14.5
• hematopoietic system phenotype
• abnormal red blood cell (MGI Ref ID J:28392)
  • presence of large inclusion bodies in red blood cells at E14.5
• decreased mean corpuscular hemoglobin (MGI Ref ID J:28392)
  • decreased mean cell hemoglobin content
• decreased mean corpuscular volume (MGI Ref ID J:28392)
• homeostasis/metabolism phenotype
• hydrops fetalis (MGI Ref ID J:28392)
  • hydrops fetalis

View Research Applications

Research Applications

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

Hba^tm1Paz related

Hematological Research
Hemoglobin Defects

Mouse/Human Gene Homologs
thalassemia, alpha

Genes & Alleles

Gene & Allele Information

Allele Symbol		Hbatm1Paz
Allele Name		targeted mutation 1, Chris Paszty
Allele Type		Targeted (knock-out)
Common Name(s)		Hba0; Hba1-2del;
Mutation Made By		Chris Paszty,   Amgen, Inc.
Strain of Origin		129S7/SvEvBrd-Hprt1<+>
ES Cell Line Name		AB1
ES Cell Line Strain		129S7/SvEvBrd-Hprt1<+>
Gene Symbol and Name		Hba, hemoglobin alpha chain complex
Chromosome		11
Molecular Note		Both of the adult hemoglobin genes, alpha 1 and alpha 2, and the region between them were deleted and replaced with a neomycin resistance cassette by homologous recombination. [MGI Ref ID J:28392]

Genotyping

Genotyping Information

Genotyping Protocols

Hba^tm1Paz, STD PCR, vers. 1
NEOTD (Generic Neo), STD PCR, vers. 1

Helpful Links

Optimizing PCR Protocols

References

References

Selected Reference(s)

Paszty C; Mohandas N; Stevens ME; Loring JF; Liebhaber SA; Brion CM; Rubin EM. 1995. Lethal alpha-thalassaemia created by gene targeting in mice and its genetic rescue. Nat Genet 11(1):33-9. [PubMed: 7550311]  [MGI Ref ID J:28392]

Additional References

Paszty C; Brion CM; Manci E; Witkowska HE; Stevens ME; Mohandas N; Rubin EM. 1997. Transgenic knockout mice with exclusively human sickle hemoglobin and sickle cell disease [see comments] Science 278(5339):876-8. [PubMed: 9346488]  [MGI Ref ID J:44161]

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]

Hba^tm1Paz related

Al-Hasani K; Vadolas J; Knaupp AS; Wardan H; Voullaire L; Williamson R; Ioannou PA. 2005. A 191-kb genomic fragment containing the human alpha-globin locus can rescue alpha-thalassemic mice. Mamm Genome 16(11):847-53. [PubMed: 16284800]  [MGI Ref ID J:103573]

Archer DR; Stiles JK; Newman GW; Quarshie A; Hsu LL; Sayavongsa P; Perry J; Jackson EM; Hibbert JM. 2008. C-reactive protein and interleukin-6 are decreased in transgenic sickle cell mice fed a high protein diet. J Nutr 138(6):1148-52. [PubMed: 18492848]  [MGI Ref ID J:136372]

Banerjee T; Kuypers FA. 2004. Reactive oxygen species and phosphatidylserine externalization in murine sickle red cells. Br J Haematol 124(3):391-402. [PubMed: 14717789]  [MGI Ref ID J:88553]

Barinaga M. 1997. Mutant mice mimic human sickle cell anemia [news; comment] Science 278(5339):803-4. [PubMed: 9381190]  [MGI Ref ID J:44159]

Belcher JD; Mahaseth H; Welch TE; Otterbein LE; Hebbel RP; Vercellotti GM. 2006. Heme oxygenase-1 is a modulator of inflammation and vaso-occlusion in transgenic sickle mice. J Clin Invest 116(3):808-16. [PubMed: 16485041]  [MGI Ref ID J:106486]

Champion HC; Bivalacqua TJ; Takimoto E; Kass DA; Burnett AL. 2005. Phosphodiesterase-5A dysregulation in penile erectile tissue is a mechanism of priapism. Proc Natl Acad Sci U S A 102(5):1661-6. [PubMed: 15668387]  [MGI Ref ID J:96103]

Chang JC; Ye L; Kan YW. 2006. Correction of the sickle cell mutation in embryonic stem cells. Proc Natl Acad Sci U S A 103(4):1036-40. [PubMed: 16407095]  [MGI Ref ID J:105707]

Dasgupta T; Hebbel RP; Kaul DK. 2006. Protective effect of arginine on oxidative stress in transgenic sickle mouse models. Free Radic Biol Med 41(12):1771-80. [PubMed: 17157180]  [MGI Ref ID J:116710]

Ieremia J; Blau CA. 2002. Limitations of a mouse model of sickle cell anemia. Blood Cells Mol Dis 28(2):146-51. [PubMed: 12064910]  [MGI Ref ID J:128113]

Kaul DK; Liu XD; Chang HY; Nagel RL; Fabry ME. 2004. Effect of fetal hemoglobin on microvascular regulation in sickle transgenic-knockout mice. J Clin Invest 114(8):1136-45. [PubMed: 15489961]  [MGI Ref ID J:93424]

Kiefmann R; Rifkind JM; Nagababu E; Bhattacharya J. 2008. Red blood cells induce hypoxic lung inflammation. Blood 111(10):5205-14. [PubMed: 18270324]  [MGI Ref ID J:135569]

Levasseur DN; Ryan TM; Pawlik KM; Townes TM. 2003. Correction of a mouse model of sickle cell disease: lentiviral/antisickling beta-globin gene transduction of unmobilized, purified hematopoietic stem cells. Blood 102(13):4312-9. [PubMed: 12933581]  [MGI Ref ID J:134982]

Mi T; Abbasi S; Zhang H; Uray K; Chunn JL; Xia LW; Molina JG; Weisbrodt NW; Kellems RE; Blackburn MR; Xia Y. 2008. Excess adenosine in murine penile erectile tissues contributes to priapism via A2B adenosine receptor signaling. J Clin Invest 118(4):1491-501. [PubMed: 18340377]  [MGI Ref ID J:135978]

Noguchi CT; Gladwin M; Diwan B; Merciris P; Smith R; Yu X; Buzard G; Fitzhugh A; Keefer LK; Schechter AN; Mohandas N. 2001. Pathophysiology of a sickle cell trait mouse model: human alpha(beta)(S) transgenes with one mouse beta-globin allele. Blood Cells Mol Dis 27(6):971-7. [PubMed: 11831863]  [MGI Ref ID J:128124]

Paszty C; Brion CM; Manci E; Witkowska HE; Stevens ME; Mohandas N; Rubin EM. 1997. Transgenic knockout mice with exclusively human sickle hemoglobin and sickle cell disease [see comments] Science 278(5339):876-8. [PubMed: 9346488]  [MGI Ref ID J:44161]

Pritchard KA Jr; Ou J; Ou Z; Shi Y; Franciosi JP; Signorino P; Kaul S; Ackland-Berglund C; Witte K; Holzhauer S; Mohandas N; Guice KS; Oldham KT; Hillery CA. 2004. Hypoxia-induced acute lung injury in murine models of sickle cell disease. Am J Physiol Lung Cell Mol Physiol 286(4):L705-14. [PubMed: 12972407]  [MGI Ref ID J:134696]

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]

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]

Solovey A; Kollander R; Shet A; Milbauer LC; Choong S; Panoskaltsis-Mortari A; Blazar BR; Kelm RJ Jr; Hebbel RP. 2004. Endothelial cell expression of tissue factor in sickle mice is augmented by hypoxia/reoxygenation and inhibited by lovastatin. Blood 104(3):840-6. [PubMed: 15073034]  [MGI Ref ID J:92287]

Whitney JB; Russell ES. 1978. New mutants and biochemical variants: Alpha thalassemia Mouse News Lett 58:47-48.  [MGI Ref ID J:45721]

Wood KC; Hebbel RP; Granger DN. 2005. Endothelial cell NADPH oxidase mediates the cerebral microvascular dysfunction in sickle cell transgenic mice. FASEB J 19(8):989-91. [PubMed: 15923406]  [MGI Ref ID J:128246]

Wood KC; Hebbel RP; Granger DN. 2004. Endothelial cell P-selectin mediates a proinflammatory and prothrombogenic phenotype in cerebral venules of sickle cell transgenic mice. Am J Physiol Heart Circ Physiol 286(5):H1608-14. [PubMed: 14704223]  [MGI Ref ID J:95603]

de Jong K; Emerson RK; Butler J; Bastacky J; Mohandas N; Kuypers FA. 2001. Short survival of phosphatidylserine-exposing red blood cells in murine sickle cell anemia. Blood 98(5):1577-84. [PubMed: 11520810]  [MGI Ref ID J:131515]

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

Repository-Cryopreserved. Must Be Recovered. Please refer to pricing and supply notes for further information.

Supply Notes

Cryorecovery - Standard. The recovery process begins when a signed agreement form is returned to the Customer Service Department after order placement. Although results vary by strain, at least two males and two females (two pairs) will be provided, typically within 15 weeks of our receipt of the signed agreement form. If the first recovery attempt is unsuccessful or only one pair is recovered, a second recovery will be done, extending the delivery time to approximately 25 weeks. At least one member of each pair will be of known genotype and will carry the mutation if it is a mutant strain. Please note that pairs may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation of the strain. Mating schemes are sometimes modified for successful cryopreservation. Price represents a repository maintenance fee, which includes the cost of recovery of the strain from the cryopreservation resource and the periodic replacement of the frozen embryos used for recovery. 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.

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
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Tel: 800.422.6423 or 207.288.5845
Fax: 207.288.6150
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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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