JAX Mouse Strain Datasheet - 003342

STOCK Hba^tm1Paz Hbb^tm1Tow Tg(HBA-HBBs)41Paz/J

Stock No:: 003342 |; Berkeley model

Repository Live

Overview

Also Known As: Berkeley model, sickle cell anemia

Mice homozygous for the alpha-globin null allele, homozygous for the beta-globin null allele and carrying the sickle transgene (Hba^0/0 Hbb^0/0 Tg(Hu-miniLCRα1^Gγ^Aγδβ^S) are called sickle cell mice (Berkeley model). These mice display the major genetic, hematologic and histopathologic features observed in humans with sickle cell anemia and may be useful in studying sickle cell disease.

Donating Investigator

Dr. Chris Paszty, Amgen, Inc.

Genetic overview

Genetic Background	Generation
	N1F7G24 (10-DEC-13)

Hba^tm1Paz

Allele Type	Gene Symbol	Gene Name
Targeted (Null/Knockout)	Hba	hemoglobin alpha chain complex

Hbb^tm1Tow

Allele Type	Gene Symbol	Gene Name
Targeted (Null/Knockout)	Hbb	hemoglobin beta chain complex

Tg(HBA-HBBs)41Paz

Allele Type
Transgenic (Humanized sequence, Inserted expressed sequence)

View Genetics

Research Applications

Hematological Research

View All Research Applications

Base Price

Starting at:

$333.00 Domestic price for female

$666.00 Domestic price for breeder pair

View Price List

Details

Detailed Description

These mice harbor
1) the Hba^tm1Paz null mutation (also called Hba⁰ ; designed with both of the adult hemoglobin genes [α1 and α2] deleted),
2) the Hbb^tm1Tow null mutation (also called Hbb⁰ ; designed with deletion of the entire hemoglobin beta-β1 [major] and the 5' portion of the hemoglobin beta-β2 [minor]),
3) the Tg(HBA-HBBs)41Paz transgene (also called Tg(Hu-miniLCRα1^Gγ^Aγδβ^S); designed with the human sequences encoding the hemoglobin subunits alpha 1 (HBA1), gamma 2 (HBG2), gamma (HBG1), delta (HBD), and the beta sickle allele (HBB^S), and the locus control region (LCR).

Mice homozygous for the alpha-globin null allele, homozygous for the beta-globin null allele and carrying the sickle transgene (Hba^0/0 Hbb^0/0 Tg(Hu-miniLCRα1^Gγ^Aγδβ^S) are called sickle cell mice (Berkeley model). They exclusively express human sickle hemoglobin, and do not express mouse Hba or Hbb. Although chronically anemic, most of these mice survive for 2 to 9 months and are fertile. A significant percentage of sickle cell mice do not survive to adulthood. These mice display the major genetic, hematologic and histopathologic features observed in humans with sickle cell anemia; including irreversibly sickled red blood cells, anemia and multiorgan pathology. Typically, ~20% of sickling mutant mice die between weaning and 14 weeks of age.

Development

The Hba^tm1Paz null mutation (also called Hba⁰) was designed by Dr. Chris Paszty to have both of the endogenous adult hemoglobin genes (α1 and α2) deleted and replaced with a neo cassette.

The Hbb^tm1Tow null mutation (also called Hbb⁰) was designed by Dr. Timothy Townes to have the endogenous hemoglobin beta sequences (the entire hemoglobin beta-β1 [major] and the 5' portion of the hemoglobin beta-β2 [minor]) deleted and replaced with a neo cassette.

The Tg(HBA-HBBs)41Paz transgene (also called Tg(Hu-miniLCRα1^Gγ^Aγδβ^S) was designed by Dr. Chris Paszty to have sequences encoding the human hemoglobin subunits alpha 1 (HBA1), gamma 2 (HBG2), gamma (HBG1), delta (HBD), and the beta sickle allele (HBB^S), as well as the locus control region (LCR). The HBB^S sequence contains an A-to-T transversion mutation in HBB codon six (amino acid change from glutamic acid to valine; E6V). The transgene promoter is multiple; from alpha and beta globin human loci. The transgene was injected into fertilized FVB/N mouse eggs.

Breeding the above mice together created the triple mutant mice - Tg(Hu-miniLCRα1^Gγ^Aγδβ^S Hba⁰ Hbb⁰. The STOCK background of the triple mutant strain is a mixture of FVB/N, 129, DBA/2, Black Swiss and >50% C57BL/6 genomes. It was backcrossed to C57BL/6J one generation after importation to The Jackson Laboratory.

Expression Data

Expressed Gene	HBA1, hemoglobin subunit alpha 1, human
Expressed Gene	HBB, hemoglobin subunit beta, human
Expressed Gene	HBD, hemoglobin subunit delta, human
Expressed Gene	HBG1, hemoglobin subunit gamma 1, human
Expressed Gene	HBG2, hemoglobin subunit gamma 2, human
Site of Expression

Control Suggestions

Homozygous for Hba^tm1Paz, Heterozygous for Hbb^tm1Tow, Hemizygous for Tg(HBA-HBBs)41Paz (non-sickling females from the colony)

Approximate Controls

000664 C57BL/6J

Additional Information

Considerations for Choosing Controls

Selected 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: J:44161

View All References

Genetics

Hba^tm1Paz

Allele Symbol: Hba^tm1Paz

Allele Name	targeted mutation 1, Chris Paszty
Allele Type	Targeted (Null/Knockout)
Allele Synonym(s)	Hba⁰; Hba^1-2del
Gene Symbol and Name	Hba, hemoglobin alpha chain complex
Gene Synonym(s)
Strain of Origin	129S7/SvEvBrd-Hprt<+>
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.
Mutations Made By	Dr. Chris Paszty, Amgen, Inc.

Hbb^tm1Tow

Allele Symbol: Hbb^tm1Tow

Allele Name	targeted mutation 1, Timothy Townes
Allele Type	Targeted (Null/Knockout)
Allele Synonym(s)	Hbb⁰; Hbb^th3; Hbb^tm1Tmt
Gene Symbol and Name	Hbb, hemoglobin beta chain complex
Gene Synonym(s)
Strain of Origin	129S2/SvPas
Chromosome	7
Molecular Note	A genomic fragment encompassing all of Hbb-b1 and a 5' portion of Hbb-b2 was replaced with a neo cassette inserted by homologous recombination.
Mutations Made By	Timothy Townes, University of Alabama School of Medicine

Tg(HBA-HBBs)41Paz

Allele Symbol: Tg(HBA-HBBs)41Paz

Allele Name	transgene insertion 41, Chris Paszty
Allele Type	Transgenic (Humanized sequence, Inserted expressed sequence)
Allele Synonym(s)	Tg(Hu-miniLCRalpha1^Ggamma^Agammadeltabeta^S); miniLCRalpha1^Ggamma^Agammadeltabeta^S
Gene Symbol and Name	Tg(HBA-HBBs)41Paz, transgene insertion 41, Chris Paszty
Gene Synonym(s)	BERK; Tg(Hu-miniLCRalpha1^Ggamma^Agammadeltabeta^S)
Promoter	HBA1, hemoglobin subunit alpha 1, human
Promoter	HBB, hemoglobin subunit beta, human
Expressed Gene	HBA1, hemoglobin subunit alpha 1, human
Expressed Gene	HBB, hemoglobin subunit beta, human
Expressed Gene	HBD, hemoglobin subunit delta, human
Expressed Gene	HBG1, hemoglobin subunit gamma 1, human
Expressed Gene	HBG2, hemoglobin subunit gamma 2, human
Strain of Origin	FVB/N
Chromosome	UN
General Note	In conjunction with Hba^tm1Paz and Hbb^tm1Tmt, transgenic mice express exclusively human sickle hemoglobin. These mice do not express mouse Hba and Hbb, but do express human HBA and HBB. Although chronically anemic, most of these mice survive for 2 to 9 months and are fertile. A significant percentage of sickle cell mice do not survive to adulthood. These mice display the major genetic, hematologic and histopathologic features found in humans with sickle cell disease: irreversibly sickled red cells, anemia, and multiorgan pathology.
Molecular Note	The transgene contains sequences encoding the human proteins HBA1 (hemoglobin, alpha 1), HBG2 (hemoglobin, gamma G, fetal component), HBG1 (hemoglobin, gamma A, fetal component), HBD (hemoglobin, delta), and HBB^S (hemoglobin, beta, sickle allele), and the locus control region (LCR). The HBB^S allele contains an A to T transversion mutation in the sixth codon of HBB which causes an amino acid change from Glu to Val. The transgene promoter is multiple: from alpha and beta globin human loci. Transgenic mice express human alpha hemoglobin, gamma hemoglobin, and sickle cell hemoglobin.
Mutations Made By	Dr. Chris Paszty, Amgen, Inc.

Disease/Phenotype

Disease Terms

Research Areas By Genotype

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

Hematological Research
- Sickle Cell Anemia

Genotype: HBB related

Hematological Research
- Hemoglobin Defects

Genotype: Hba^tm1Paz related

Hematological Research
- Hemoglobin Defects

Genotype: Hbb^tm1Tow related

Hematological Research
- Hemoglobin Defects

Mammalian Phenotype Terms by Genotype

Genotype: Hba^tm1Paz/Hba^tm1Paz Hbb^tm1Tow/Hbb^tm1Tow Tg(HBA-HBBs)41Paz/0
involves: 129 * Black Swiss * C57BL/6 * DBA/2 * FVB/N

reproductive system phenotype

abnormal penile erection
- however, treatment with an Adora2b antagonist or PEG-ADA reduces priapic activity
- mice exhibit increased corpus cavernosal smooth muscle relaxation in response to nerve stimulation

priapism
- however, treatment with an Adora2b antagonist or PEG-ADA reduces priapic activity
- mice exhibit priapism that is associated with elevated levels of adenosine

Genotype: Hba^tm1Paz/Hba^tm1Paz Hbb^tm1Tow/Hbb^tm1Tow Tg(HBA-HBBs)41Paz/?
involves: 129S2/SvPas * 129S7/SvEvBrd * Black Swiss * C57BL/6 * DBA/2* FVB/N

mortality/aging

neonatal lethality, incomplete penetrance
- many pups turn purple and die within a few hours of birth, however, mice that survive live to become adults (reaching at least 7 months of age)

hematopoietic system phenotype

abnormal erythrocyte morphology
- erythrocytes have increased dynamic rigidity

abnormal erythrocyte osmotic lysis
- erythrocytes have decreased osmotic fragility

abnormal hemoglobin
- erythrocytes contain an excess of alpha globin chain synthesis

anemia

anisopoikilocytosis
- sickle cell shapes are observed at a frequency of 5-10% in oxygenated blood

decreased hematocrit
- average hematocrit levels are 65% of control at 3-7 months of age

decreased mean corpuscular hemoglobin

decreased mean corpuscular hemoglobin concentration

decreased mean corpuscular volume

increased spleen weight
- weight is increased 13-fold as compared to control

reticulocytosis
- reticulocyte counts are elevated at 3-7 months of age

spleen vascular congestion
- congested sinusoidal channels are observed in spleen

homeostasis/metabolism phenotype

hypoxia
- cause of death in some newborn mice

increased kidney iron level
- iron deposits found in the tubular epithelium of the kidney

increased liver iron level
- iron deposits found in Kupffer cells of liver

cardiovascular system phenotype

abnormal kidney blood vessel morphology
- kidney infarction

abnormal liver vasculature morphology
- liver infarction

abnormal lung vasculature morphology
- lung infarction

increased heart weight
- weight is increased 2-fold as compared to control

spleen vascular congestion
- congested sinusoidal channels are observed in spleen

renal/urinary system phenotype

abnormal kidney blood vessel morphology
- kidney infarction

increased kidney iron level
- iron deposits found in the tubular epithelium of the kidney

increased kidney weight
- weight is increased 2-fold as compared to control

kidney atrophy

kidney cysts

renal fibrosis

immune system phenotype

increased spleen weight
- weight is increased 13-fold as compared to control

spleen vascular congestion
- congested sinusoidal channels are observed in spleen

liver/biliary system phenotype

abnormal liver vasculature morphology
- liver infarction

increased liver iron level
- iron deposits found in Kupffer cells of liver

respiratory system phenotype

abnormal lung vasculature morphology
- lung infarction

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: J:44161

Additional References

Barinaga M. 1997. Mutant mice mimic human sickle cell anemia [news; comment] Science 278(5339):803-4. PubMed: 9381190 MGI: J:44159
Ciavatta DJ; Ryan TM; Farmer SC; Townes TM. 1995. Mouse model of human beta zero thalassemia: targeted deletion of the mouse beta maj- and beta min-globin genes in embryonic stem cells. Proc Natl Acad Sci U S A 92(20):9259-63. PubMed: 7568113 MGI: J:29087
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: J:44160

Additional - 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: 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: J:136372
Arumugam PI; Mullins ES; Shanmukhappa SK; Monia BP; Loberg A; Shaw MA; Rizvi T; Wansapura J; Degen JL; Malik P. 2015. Genetic diminution of circulating prothrombin ameliorates multiorgan pathologies in sickle cell disease mice. Blood 126(15):1844-55. PubMed: 26286849 MGI: J:230254
Bakeer N; James J; Roy S; Wansapura J; Shanmukhappa SK; Lorenz JN; Osinska H; Backer K; Huby AC; Shrestha A; Niss O; Fleck R; Quinn CT; Taylor MD; Purevjav E; Aronow BJ; Towbin JA; Malik P. 2016. Sickle cell anemia mice develop a unique cardiomyopathy with restrictive physiology. Proc Natl Acad Sci U S A 113(35):E5182-91. PubMed: 27503873 MGI: J:235608
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: J:88553
Barazia A; Li J; Kim K; Shabrani N; Cho J. 2015. Hydroxyurea with AKT2 inhibition decreases vaso-occlusive events in sickle cell disease mice. Blood 126(22):2511-7. PubMed: 26265698 MGI: J:230085
Barinaga M. 1997. Mutant mice mimic human sickle cell anemia [news; comment] Science 278(5339):803-4. PubMed: 9381190 MGI: 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: J:106486
Bivalacqua TJ; Musicki B; Hsu LL; Berkowitz DE; Champion HC; Burnett AL. 2013. Sildenafil citrate-restored eNOS and PDE5 regulation in sickle cell mouse penis prevents priapism via control of oxidative/nitrosative stress. PLoS One 8(7):e68028. PubMed: 23844149 MGI: J:204301
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: J:96103
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: J:164535
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: J:105707
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: J:189104
Chen G; Zhang D; Fuchs TA; Manwani D; Wagner DD; Frenette PS. 2014. Heme-induced neutrophil extracellular traps contribute to the pathogenesis of sickle cell disease. Blood 123(24):3818-27. PubMed: 24620350 MGI: J:210886
Dasgupta T; Fabry ME; Kaul DK. 2010. Antisickling property of fetal hemoglobin enhances nitric oxide bioavailability and ameliorates organ oxidative stress in transgenic-knockout sickle mice. Am J Physiol Regul Integr Comp Physiol 298(2):R394-402. PubMed: 20007516 MGI: J:156179
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: J:116710
Eiymo Mwa Mpollo MS; Brandt EB; Shanmukhappa SK; Arumugam PI; Tiwari S; Loberg A; Pillis D; Rizvi T; Lindsey M; Jonck B; Carmeliet P; Kalra VK; Le Cras TD; Ratner N; Wills-Karp M; Hershey GK; Malik P. 2016. Placenta growth factor augments airway hyperresponsiveness via leukotrienes and IL-13. J Clin Invest 126(2):571-84. PubMed: 26690703 MGI: J:231182
Fabry ME; Suzuka SM; Weinberg RS; Lawrence C; Factor SM; Gilman JG; Costantini F; Nagel RL. 2001. Second generation knockout sickle mice: the effect of HbF. Blood 97(2):410-8. PubMed: 11154217 MGI: J:66961
Gavins FN; Russell J; Senchenkova EL; De Almeida Paula L; Damazo AS; Esmon CT; Kirchhofer D; Hebbel RP; Granger DN. 2011. Mechanisms of enhanced thrombus formation in cerebral microvessels of mice expressing hemoglobin-S. Blood 117(15):4125-33. PubMed: 21304105 MGI: J:172840
Gutsaeva DR; Montero-Huerta P; Parkerson JB; Yerigenahally SD; Ikuta T; Head CA. 2014. Molecular mechanisms underlying synergistic adhesion of sickle red blood cells by hypoxia and low nitric oxide bioavailability. Blood 123(12):1917-26. PubMed: 24429338 MGI: J:209498
Gutsaeva DR; Parkerson JB; Yerigenahally SD; Kurz JC; Schaub RG; Ikuta T; Head CA. 2011. Inhibition of cell adhesion by anti-P-selectin aptamer: a new potential therapeutic agent for sickle cell disease. Blood 117(2):727-35. PubMed: 20926770 MGI: J:168427
Hanson MS; Xu H; Flewelen TC; Holzhauer SL; Retherford D; Jones DW; Frei AC; Pritchard KA Jr; Hillery CA; Hogg N; Wandersee NJ. 2013. A novel hemoglobin-binding peptide reduces cell-free hemoglobin in murine hemolytic anemia. Am J Physiol Heart Circ Physiol 304(2):H328-36. PubMed: 23125208 MGI: J:192837
Hebbel RP; Vercellotti GM; Pace BS; Solovey AN; Kollander R; Abanonu CF; Nguyen J; Vineyard JV; Belcher JD; Abdulla F; Osifuye S; Eaton JW; Kelm RJ Jr; Slungaard A. 2010. The HDAC inhibitors trichostatin A and suberoylanilide hydroxamic acid exhibit multiple modalities of benefit for the vascular pathobiology of sickle transgenic mice. Blood 115(12):2483-90. PubMed: 20053759 MGI: J:159262
Hidalgo A; Chang J; Jang JE; Peired AJ; Chiang EY; Frenette PS. 2009. Heterotypic interactions enabled by polarized neutrophil microdomains mediate thromboinflammatory injury. Nat Med 15(4):384-91. PubMed: 19305412 MGI: J:149370
Hsu LL; Champion HC; Campbell-Lee SA; Bivalacqua TJ; Manci EA; Diwan BA; Schimel DM; Cochard AE; Wang X; Schechter AN; Noguchi CT; Gladwin MT. 2007. Hemolysis in sickle cell mice causes pulmonary hypertension due to global impairment in nitric oxide bioavailability. Blood 109(7):3088-98. PubMed: 17158223 MGI: J:145347
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: J:128113
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: J:192836
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: 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: J:135569
Kohli DR; Li Y; Khasabov SG; Gupta P; Kehl LJ; Ericson ME; Nguyen J; Gupta V; Hebbel RP; Simone DA; Gupta K. 2010. Pain-related behaviors and neurochemical alterations in mice expressing sickle hemoglobin: modulation by cannabinoids. Blood 116(3):456-65. PubMed: 20304807 MGI: J:162824
Lagoda G; Sezen SF; Hurt KJ; Cabrini MR; Mohanty DK; Burnett AL. 2014. Sustained nitric oxide (NO)-releasing compound reverses dysregulated NO signal transduction in priapism. FASEB J 28(1):76-84. PubMed: 24076963 MGI: J:206623
Lebensburger JD; Howard T; Hu Y; Pestina TI; Gao G; Johnson M; Zakharenko SS; Ware RE; Tuomanen EI; Persons DA; Rosch JW. 2012. Hydroxyurea therapy of a murine model of sickle cell anemia inhibits the progression of pneumococcal disease by down-modulating E-selectin. Blood 119(8):1915-21. PubMed: 22130804 MGI: J:181749
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: J:134982
Li J; Kim K; Hahm E; Molokie R; Hay N; Gordeuk VR; Du X; Cho J. 2014. Neutrophil AKT2 regulates heterotypic cell-cell interactions during vascular inflammation. J Clin Invest 124(4):1483-96. PubMed: 24642468 MGI: J:209590
Liu S; McConnell SC; Ryan TM. 2013. Erythropoiesis in the absence of adult hemoglobin. Mol Cell Biol 33(11):2241-51. PubMed: 23530053 MGI: J:204029
Manci EA; Hillery CA; Bodian CA; Zhang ZG; Lutty GA; Coller BS. 2006. Pathology of Berkeley sickle cell mice: similarities and differences with human sickle cell disease. Blood 107(4):1651-8. PubMed: 16166585 MGI: J:129356
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: J:174901
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: J:135978
Musicki B; Zhang Y; Chen H; Brown TR; Zirkin BR; Burnett AL. 2015. Mechanism of testosterone deficiency in the transgenic sickle cell mouse. PLoS One 10(5):e0128694. PubMed: 26023917 MGI: J:237731
Ning C; Wen J; Zhang Y; Dai Y; Wang W; Zhang W; Qi L; Grenz A; Eltzschig HK; Blackburn MR; Kellems RE; Xia Y. 2014. Excess adenosine A2B receptor signaling contributes to priapism through HIF-1alpha mediated reduction of PDE5 gene expression. FASEB J 28(6):2725-35. PubMed: 24614760 MGI: J:216540
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: J:128124
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: J:28392
Peranteau WH; Hayashi S; Abdulmalik O; Chen Q; Merchant A; Asakura T; Flake AW. 2015. Correction of murine hemoglobinopathies by prenatal tolerance induction and postnatal nonmyeloablative allogeneic BM transplants. Blood 126(10):1245-54. PubMed: 26124498 MGI: J:226447
Prado GN; Romero JR; Rivera A. 2013. Endothelin-1 receptor antagonists regulate cell surface-associated protein disulfide isomerase in sickle cell disease. FASEB J 27(11):4619-29. PubMed: 23913858 MGI: J:203687
Pritchard KA Jr; Feroah TR; Nandedkar SD; Holzhauer SL; Hutchins W; Schulte ML; Strunk RC; Debaun MR; Hillery CA. 2012. Effects of experimental asthma on inflammation and lung mechanics in sickle cell mice. Am J Respir Cell Mol Biol 46(3):389-96. PubMed: 22033263 MGI: J:194579
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: 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: 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: 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: 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: J:92287
Sparkenbaugh EM; Chantrathammachart P; Chandarajoti K; Mackman N; Key NS; Pawlinski R. 2016. Thrombin-independent contribution of tissue factor to inflammation and cardiac hypertrophy in a mouse model of sickle cell disease. Blood 127(10):1371-3. PubMed: 26817955 MGI: J:232634
Sparkenbaugh EM; Chantrathammachart P; Mickelson J; van Ryn J; Hebbel RP; Monroe DM; Mackman N; Key NS; Pawlinski R. 2014. Differential contribution of FXa and thrombin to vascular inflammation in a mouse model of sickle cell disease. Blood 123(11):1747-56. PubMed: 24449213 MGI: J:209655
Sun K; Zhang Y; Bogdanov MV; Wu H; Song A; Li J; Dowhan W; Idowu M; Juneja HS; Molina JG; Blackburn MR; Kellems RE; Xia Y. 2015. Elevated adenosine signaling via adenosine A2B receptor induces normal and sickle erythrocyte sphingosine kinase 1 activity. Blood 125(10):1643-52. PubMed: 25587035 MGI: J:221918
Sundaram N; Tailor A; Mendelsohn L; Wansapura J; Wang X; Higashimoto T; Pauciulo MW; Gottliebson W; Kalra VK; Nichols WC; Kato GJ; Malik P. 2010. High levels of placenta growth factor in sickle cell disease promote pulmonary hypertension. Blood 116(1):109-12. PubMed: 20335221 MGI: J:162823
Vincent L; Vang D; Nguyen J; Gupta M; Luk K; Ericson ME; Simone DA; Gupta K. 2013. Mast cell activation contributes to sickle cell pathobiology and pain in mice. Blood 122(11):1853-62. PubMed: 23775718 MGI: J:202290
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: J:141719
Wallace HA; Marques-Kranc F; Richardson M; Luna-Crespo F; Sharpe JA; Hughes J; Wood WG; Higgs DR; Smith AJ. 2007. Manipulating the mouse genome to engineer precise functional syntenic replacements with human sequence. Cell 128(1):197-209. PubMed: 17218265 MGI: J:117887
Wang L; Almeida LE; de Souza Batista CM; Khaibullina A; Xu N; Albani S; Guth KA; Seo JS; Quezado M; Quezado ZM. 2016. Cognitive and behavior deficits in sickle cell mice are associated with profound neuropathologic changes in hippocampus and cerebellum. Neurobiol Dis 85:60-72. PubMed: 26462816 MGI: J:228649
Wen J; Jiang X; Dai Y; Zhang Y; Tang Y; Sun H; Mi T; Phatarpekar PV; Kellems RE; Blackburn MR; Xia Y. 2010. Increased adenosine contributes to penile fibrosis, a dangerous feature of priapism, via A2B adenosine receptor signaling. FASEB J 24(3):740-9. PubMed: 19858092 MGI: J:158034
Whitney JB; Russell ES. 1978. New mutants and biochemical variants: Alpha thalassemia Mouse News Lett 58:47-48. MGI: J:45721
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: J:95603
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: J:128246
Xu J; Peng C; Sankaran VG; Shao Z; Esrick EB; Chong BG; Ippolito GC; Fujiwara Y; Ebert BL; Tucker PW; Orkin SH. 2011. Correction of sickle cell disease in adult mice by interference with fetal hemoglobin silencing. Science 334(6058):993-6. PubMed: 21998251 MGI: J:177861
Zhang Y; Dai Y; Wen J; Zhang W; Grenz A; Sun H; Tao L; Lu G; Alexander DC; Milburn MV; Carter-Dawson L; Lewis DE; Zhang W; Eltzschig HK; Kellems RE; Blackburn MR; Juneja HS; Xia Y. 2011. Detrimental effects of adenosine signaling in sickle cell disease. Nat Med 17(1):79-86. PubMed: 21170046 MGI: J:168473
Zhao Y; Schwartz EA; Palmer GM; Zennadi R. 2016. MEK1/2 inhibitors reverse acute vascular occlusion in mouse models of sickle cell disease. FASEB J 30(3):1171-86. PubMed: 26631480 MGI: J:230900
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: J:131515

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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: J:136372
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Bakeer N; James J; Roy S; Wansapura J; Shanmukhappa SK; Lorenz JN; Osinska H; Backer K; Huby AC; Shrestha A; Niss O; Fleck R; Quinn CT; Taylor MD; Purevjav E; Aronow BJ; Towbin JA; Malik P. 2016. Sickle cell anemia mice develop a unique cardiomyopathy with restrictive physiology. Proc Natl Acad Sci U S A 113(35):E5182-91. PubMed: 27503873 MGI: J:235608
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: J:88553
Barazia A; Li J; Kim K; Shabrani N; Cho J. 2015. Hydroxyurea with AKT2 inhibition decreases vaso-occlusive events in sickle cell disease mice. Blood 126(22):2511-7. PubMed: 26265698 MGI: J:230085
Barinaga M. 1997. Mutant mice mimic human sickle cell anemia [news; comment] Science 278(5339):803-4. PubMed: 9381190 MGI: 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: J:106486
Bivalacqua TJ; Musicki B; Hsu LL; Berkowitz DE; Champion HC; Burnett AL. 2013. Sildenafil citrate-restored eNOS and PDE5 regulation in sickle cell mouse penis prevents priapism via control of oxidative/nitrosative stress. PLoS One 8(7):e68028. PubMed: 23844149 MGI: J:204301
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: J:96103
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: J:164535
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: J:105707
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: J:189104
Chen G; Zhang D; Fuchs TA; Manwani D; Wagner DD; Frenette PS. 2014. Heme-induced neutrophil extracellular traps contribute to the pathogenesis of sickle cell disease. Blood 123(24):3818-27. PubMed: 24620350 MGI: J:210886
Ciavatta DJ; Ryan TM; Farmer SC; Townes TM. 1995. Mouse model of human beta zero thalassemia: targeted deletion of the mouse beta maj- and beta min-globin genes in embryonic stem cells. Proc Natl Acad Sci U S A 92(20):9259-63. PubMed: 7568113 MGI: J:29087
Dasgupta T; Fabry ME; Kaul DK. 2010. Antisickling property of fetal hemoglobin enhances nitric oxide bioavailability and ameliorates organ oxidative stress in transgenic-knockout sickle mice. Am J Physiol Regul Integr Comp Physiol 298(2):R394-402. PubMed: 20007516 MGI: J:156179
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: J:116710
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Gavins FN; Russell J; Senchenkova EL; De Almeida Paula L; Damazo AS; Esmon CT; Kirchhofer D; Hebbel RP; Granger DN. 2011. Mechanisms of enhanced thrombus formation in cerebral microvessels of mice expressing hemoglobin-S. Blood 117(15):4125-33. PubMed: 21304105 MGI: J:172840
Gutsaeva DR; Parkerson JB; Yerigenahally SD; Kurz JC; Schaub RG; Ikuta T; Head CA. 2011. Inhibition of cell adhesion by anti-P-selectin aptamer: a new potential therapeutic agent for sickle cell disease. Blood 117(2):727-35. PubMed: 20926770 MGI: J:168427
Hanson MS; Xu H; Flewelen TC; Holzhauer SL; Retherford D; Jones DW; Frei AC; Pritchard KA Jr; Hillery CA; Hogg N; Wandersee NJ. 2013. A novel hemoglobin-binding peptide reduces cell-free hemoglobin in murine hemolytic anemia. Am J Physiol Heart Circ Physiol 304(2):H328-36. PubMed: 23125208 MGI: J:192837
Hebbel RP; Vercellotti GM; Pace BS; Solovey AN; Kollander R; Abanonu CF; Nguyen J; Vineyard JV; Belcher JD; Abdulla F; Osifuye S; Eaton JW; Kelm RJ Jr; Slungaard A. 2010. The HDAC inhibitors trichostatin A and suberoylanilide hydroxamic acid exhibit multiple modalities of benefit for the vascular pathobiology of sickle transgenic mice. Blood 115(12):2483-90. PubMed: 20053759 MGI: J:159262
Hidalgo A; Chang J; Jang JE; Peired AJ; Chiang EY; Frenette PS. 2009. Heterotypic interactions enabled by polarized neutrophil microdomains mediate thromboinflammatory injury. Nat Med 15(4):384-91. PubMed: 19305412 MGI: J:149370
Hsu LL; Champion HC; Campbell-Lee SA; Bivalacqua TJ; Manci EA; Diwan BA; Schimel DM; Cochard AE; Wang X; Schechter AN; Noguchi CT; Gladwin MT. 2007. Hemolysis in sickle cell mice causes pulmonary hypertension due to global impairment in nitric oxide bioavailability. Blood 109(7):3088-98. PubMed: 17158223 MGI: J:145347
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: J:128113
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: J:192836
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: 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: J:135569
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Lagoda G; Sezen SF; Hurt KJ; Cabrini MR; Mohanty DK; Burnett AL. 2014. Sustained nitric oxide (NO)-releasing compound reverses dysregulated NO signal transduction in priapism. FASEB J 28(1):76-84. PubMed: 24076963 MGI: J:206623
Lebensburger JD; Howard T; Hu Y; Pestina TI; Gao G; Johnson M; Zakharenko SS; Ware RE; Tuomanen EI; Persons DA; Rosch JW. 2012. Hydroxyurea therapy of a murine model of sickle cell anemia inhibits the progression of pneumococcal disease by down-modulating E-selectin. Blood 119(8):1915-21. PubMed: 22130804 MGI: J:181749
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: J:134982
Li J; Kim K; Hahm E; Molokie R; Hay N; Gordeuk VR; Du X; Cho J. 2014. Neutrophil AKT2 regulates heterotypic cell-cell interactions during vascular inflammation. J Clin Invest 124(4):1483-96. PubMed: 24642468 MGI: J:209590
Liu S; McConnell SC; Ryan TM. 2013. Erythropoiesis in the absence of adult hemoglobin. Mol Cell Biol 33(11):2241-51. PubMed: 23530053 MGI: J:204029
Manci EA; Hillery CA; Bodian CA; Zhang ZG; Lutty GA; Coller BS. 2006. Pathology of Berkeley sickle cell mice: similarities and differences with human sickle cell disease. Blood 107(4):1651-8. PubMed: 16166585 MGI: J:129356
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: J:170380
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: J:174901
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: J:135978
Musicki B; Zhang Y; Chen H; Brown TR; Zirkin BR; Burnett AL. 2015. Mechanism of testosterone deficiency in the transgenic sickle cell mouse. PLoS One 10(5):e0128694. PubMed: 26023917 MGI: J:237731
Nandedkar SD; Feroah TR; Hutchins W; Weihrauch D; Konduri KS; Wang J; Strunk RC; DeBaun MR; Hillery CA; Pritchard KA. 2008. Histopathology of experimentally induced asthma in a murine model of sickle cell disease. Blood 112(6):2529-38. PubMed: 18579795 MGI: J:138890
Ning C; Wen J; Zhang Y; Dai Y; Wang W; Zhang W; Qi L; Grenz A; Eltzschig HK; Blackburn MR; Kellems RE; Xia Y. 2014. Excess adenosine A2B receptor signaling contributes to priapism through HIF-1alpha mediated reduction of PDE5 gene expression. FASEB J 28(6):2725-35. PubMed: 24614760 MGI: J:216540
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: J:128124
Peranteau WH; Hayashi S; Abdulmalik O; Chen Q; Merchant A; Asakura T; Flake AW. 2015. Correction of murine hemoglobinopathies by prenatal tolerance induction and postnatal nonmyeloablative allogeneic BM transplants. Blood 126(10):1245-54. PubMed: 26124498 MGI: J:226447
Prado GN; Romero JR; Rivera A. 2013. Endothelin-1 receptor antagonists regulate cell surface-associated protein disulfide isomerase in sickle cell disease. FASEB J 27(11):4619-29. PubMed: 23913858 MGI: J:203687
Pritchard KA Jr; Feroah TR; Nandedkar SD; Holzhauer SL; Hutchins W; Schulte ML; Strunk RC; Debaun MR; Hillery CA. 2012. Effects of experimental asthma on inflammation and lung mechanics in sickle cell mice. Am J Respir Cell Mol Biol 46(3):389-96. PubMed: 22033263 MGI: J:194579
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: J:134696
Ramos P; Casu C; Gardenghi S; Breda L; Crielaard BJ; Guy E; Marongiu MF; Gupta R; Levine RL; Abdel-Wahab O; Ebert BL; Van Rooijen N; Ghaffari S; Grady RW; Giardina PJ; Rivella S. 2013. Macrophages support pathological erythropoiesis in polycythemia vera and beta-thalassemia. Nat Med 19(4):437-45. PubMed: 23502961 MGI: J:197988
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: J:88563
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: 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: J:92287
Sparkenbaugh EM; Chantrathammachart P; Chandarajoti K; Mackman N; Key NS; Pawlinski R. 2016. Thrombin-independent contribution of tissue factor to inflammation and cardiac hypertrophy in a mouse model of sickle cell disease. Blood 127(10):1371-3. PubMed: 26817955 MGI: J:232634
Sparkenbaugh EM; Chantrathammachart P; Mickelson J; van Ryn J; Hebbel RP; Monroe DM; Mackman N; Key NS; Pawlinski R. 2014. Differential contribution of FXa and thrombin to vascular inflammation in a mouse model of sickle cell disease. Blood 123(11):1747-56. PubMed: 24449213 MGI: J:209655
Sun K; Zhang Y; Bogdanov MV; Wu H; Song A; Li J; Dowhan W; Idowu M; Juneja HS; Molina JG; Blackburn MR; Kellems RE; Xia Y. 2015. Elevated adenosine signaling via adenosine A2B receptor induces normal and sickle erythrocyte sphingosine kinase 1 activity. Blood 125(10):1643-52. PubMed: 25587035 MGI: J:221918
Sundaram N; Tailor A; Mendelsohn L; Wansapura J; Wang X; Higashimoto T; Pauciulo MW; Gottliebson W; Kalra VK; Nichols WC; Kato GJ; Malik P. 2010. High levels of placenta growth factor in sickle cell disease promote pulmonary hypertension. Blood 116(1):109-12. PubMed: 20335221 MGI: J:162823
Szuber N; Buss JL; Soe-Lin S; Felfly H; Trudel M; Ponka P. 2008. Alternative treatment paradigm for thalassemia using iron chelators. Exp Hematol 36(7):773-85. PubMed: 18456387 MGI: J:136991
Vincent L; Vang D; Nguyen J; Gupta M; Luk K; Ericson ME; Simone DA; Gupta K. 2013. Mast cell activation contributes to sickle cell pathobiology and pain in mice. Blood 122(11):1853-62. PubMed: 23775718 MGI: J:202290
Wang L; Almeida LE; de Souza Batista CM; Khaibullina A; Xu N; Albani S; Guth KA; Seo JS; Quezado M; Quezado ZM. 2016. Cognitive and behavior deficits in sickle cell mice are associated with profound neuropathologic changes in hippocampus and cerebellum. Neurobiol Dis 85:60-72. PubMed: 26462816 MGI: J:228649
Wen J; Jiang X; Dai Y; Zhang Y; Tang Y; Sun H; Mi T; Phatarpekar PV; Kellems RE; Blackburn MR; Xia Y. 2010. Increased adenosine contributes to penile fibrosis, a dangerous feature of priapism, via A2B adenosine receptor signaling. FASEB J 24(3):740-9. PubMed: 19858092 MGI: J:158034
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: J:95603
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: J:128246
Xu J; Peng C; Sankaran VG; Shao Z; Esrick EB; Chong BG; Ippolito GC; Fujiwara Y; Ebert BL; Tucker PW; Orkin SH. 2011. Correction of sickle cell disease in adult mice by interference with fetal hemoglobin silencing. Science 334(6058):993-6. PubMed: 21998251 MGI: J:177861
Zhang Y; Dai Y; Wen J; Zhang W; Grenz A; Sun H; Tao L; Lu G; Alexander DC; Milburn MV; Carter-Dawson L; Lewis DE; Zhang W; Eltzschig HK; Kellems RE; Blackburn MR; Juneja HS; Xia Y. 2011. Detrimental effects of adenosine signaling in sickle cell disease. Nat Med 17(1):79-86. PubMed: 21170046 MGI: J:168473
Zhao Y; Schwartz EA; Palmer GM; Zennadi R. 2016. MEK1/2 inhibitors reverse acute vascular occlusion in mouse models of sickle cell disease. FASEB J 30(3):1171-86. PubMed: 26631480 MGI: J:230900
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: J:131515

Additional - Tg(HBA-HBBs)41Paz related

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: J:136372
Arumugam PI; Mullins ES; Shanmukhappa SK; Monia BP; Loberg A; Shaw MA; Rizvi T; Wansapura J; Degen JL; Malik P. 2015. Genetic diminution of circulating prothrombin ameliorates multiorgan pathologies in sickle cell disease mice. Blood 126(15):1844-55. PubMed: 26286849 MGI: J:230254
Bakeer N; James J; Roy S; Wansapura J; Shanmukhappa SK; Lorenz JN; Osinska H; Backer K; Huby AC; Shrestha A; Niss O; Fleck R; Quinn CT; Taylor MD; Purevjav E; Aronow BJ; Towbin JA; Malik P. 2016. Sickle cell anemia mice develop a unique cardiomyopathy with restrictive physiology. Proc Natl Acad Sci U S A 113(35):E5182-91. PubMed: 27503873 MGI: J:235608
Barazia A; Li J; Kim K; Shabrani N; Cho J. 2015. Hydroxyurea with AKT2 inhibition decreases vaso-occlusive events in sickle cell disease mice. Blood 126(22):2511-7. PubMed: 26265698 MGI: J:230085
Barinaga M. 1997. Mutant mice mimic human sickle cell anemia [news; comment] Science 278(5339):803-4. PubMed: 9381190 MGI: J:44159
Belcher JD; Bryant CJ; Nguyen J; Bowlin PR; Kielbik MC; Bischof JC; Hebbel RP; Vercellotti GM. 2003. Transgenic sickle mice have vascular inflammation. Blood 101(10):3953-9. PubMed: 12543857 MGI: J:83445
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: J:106486
Bivalacqua TJ; Musicki B; Hsu LL; Berkowitz DE; Champion HC; Burnett AL. 2013. Sildenafil citrate-restored eNOS and PDE5 regulation in sickle cell mouse penis prevents priapism via control of oxidative/nitrosative stress. PLoS One 8(7):e68028. PubMed: 23844149 MGI: J:204301
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: J:96103
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: J:164535
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: J:105707
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: J:189104
Chen G; Zhang D; Fuchs TA; Manwani D; Wagner DD; Frenette PS. 2014. Heme-induced neutrophil extracellular traps contribute to the pathogenesis of sickle cell disease. Blood 123(24):3818-27. PubMed: 24620350 MGI: J:210886
Dasgupta T; Fabry ME; Kaul DK. 2010. Antisickling property of fetal hemoglobin enhances nitric oxide bioavailability and ameliorates organ oxidative stress in transgenic-knockout sickle mice. Am J Physiol Regul Integr Comp Physiol 298(2):R394-402. PubMed: 20007516 MGI: J:156179
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: J:116710
Eiymo Mwa Mpollo MS; Brandt EB; Shanmukhappa SK; Arumugam PI; Tiwari S; Loberg A; Pillis D; Rizvi T; Lindsey M; Jonck B; Carmeliet P; Kalra VK; Le Cras TD; Ratner N; Wills-Karp M; Hershey GK; Malik P. 2016. Placenta growth factor augments airway hyperresponsiveness via leukotrienes and IL-13. J Clin Invest 126(2):571-84. PubMed: 26690703 MGI: J:231182
Gavins FN; Russell J; Senchenkova EL; De Almeida Paula L; Damazo AS; Esmon CT; Kirchhofer D; Hebbel RP; Granger DN. 2011. Mechanisms of enhanced thrombus formation in cerebral microvessels of mice expressing hemoglobin-S. Blood 117(15):4125-33. PubMed: 21304105 MGI: J:172840
Gutsaeva DR; Montero-Huerta P; Parkerson JB; Yerigenahally SD; Ikuta T; Head CA. 2014. Molecular mechanisms underlying synergistic adhesion of sickle red blood cells by hypoxia and low nitric oxide bioavailability. Blood 123(12):1917-26. PubMed: 24429338 MGI: J:209498
Gutsaeva DR; Parkerson JB; Yerigenahally SD; Kurz JC; Schaub RG; Ikuta T; Head CA. 2011. Inhibition of cell adhesion by anti-P-selectin aptamer: a new potential therapeutic agent for sickle cell disease. Blood 117(2):727-35. PubMed: 20926770 MGI: J:168427
He Z; Russell JE. 2004. Antisickling effects of an endogenous human alpha-like globin. Nat Med 10(4):365-7. PubMed: 15034572 MGI: J:131270
Hidalgo A; Chang J; Jang JE; Peired AJ; Chiang EY; Frenette PS. 2009. Heterotypic interactions enabled by polarized neutrophil microdomains mediate thromboinflammatory injury. Nat Med 15(4):384-91. PubMed: 19305412 MGI: J:149370
Holtzclaw JD; Jack D; Aguayo SM; Eckman JR; Roman J; Hsu LL. 2004. Enhanced pulmonary and systemic response to endotoxin in transgenic sickle mice. Am J Respir Crit Care Med 169(6):687-95. PubMed: 14684557 MGI: J:132062
Hsu LL; Champion HC; Campbell-Lee SA; Bivalacqua TJ; Manci EA; Diwan BA; Schimel DM; Cochard AE; Wang X; Schechter AN; Noguchi CT; Gladwin MT. 2007. Hemolysis in sickle cell mice causes pulmonary hypertension due to global impairment in nitric oxide bioavailability. Blood 109(7):3088-98. PubMed: 17158223 MGI: J:145347
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: J:128113
Jang JE; Hidalgo A; Frenette PS. 2012. Intravenous immunoglobulins modulate neutrophil activation and vascular injury through FcgammaRIII and SHP-1. Circ Res 110(8):1057-66. PubMed: 22415018 MGI: J:212521
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: J:192836
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Also Known As: Berkeley model, sickle cell anemia

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Expression Data

Control Suggestions

Approximate Controls

Additional Information

Selected References

Hbatm1Paz

Allele Symbol: Hbatm1Paz

Hbbtm1Tow

Allele Symbol: Hbbtm1Tow

Tg(HBA-HBBs)41Paz

Allele Symbol: Tg(HBA-HBBs)41Paz

Disease Terms

Research Areas By Genotype

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

Genotype: HBB related

Genotype: Hbatm1Paz related

Genotype: Hbbtm1Tow related

Mammalian Phenotype Terms by Genotype

Genotype: Hbatm1Paz/Hbatm1Paz Hbbtm1Tow/Hbbtm1Tow Tg(HBA-HBBs)41Paz/0involves: 129 * Black Swiss * C57BL/6 * DBA/2 * FVB/N

reproductive system phenotype

Genotype: Hbatm1Paz/Hbatm1Paz Hbbtm1Tow/Hbbtm1Tow Tg(HBA-HBBs)41Paz/?involves: 129S2/SvPas * 129S7/SvEvBrd * Black Swiss * C57BL/6 * DBA/2* FVB/N

mortality/aging

hematopoietic system phenotype

homeostasis/metabolism phenotype

cardiovascular system phenotype

renal/urinary system phenotype

immune system phenotype

liver/biliary system phenotype

respiratory system phenotype

References

Additional References

Additional - Hbatm1Paz related

Additional - Hbbtm1Tow related

Additional - Tg(HBA-HBBs)41Paz related

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Cryorecovery - Pricing

Progeny testing is not required

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No Liability

Hba^tm1Paz

Allele Symbol: Hba^tm1Paz

Hbb^tm1Tow

Allele Symbol: Hbb^tm1Tow

Genotype: Hba^tm1Paz related

Genotype: Hbb^tm1Tow related

Genotype: Hba^tm1Paz/Hba^tm1Paz Hbb^tm1Tow/Hbb^tm1Tow Tg(HBA-HBBs)41Paz/0
involves: 129 * Black Swiss * C57BL/6 * DBA/2 * FVB/N

Genotype: Hba^tm1Paz/Hba^tm1Paz Hbb^tm1Tow/Hbb^tm1Tow Tg(HBA-HBBs)41Paz/?
involves: 129S2/SvPas * 129S7/SvEvBrd * Black Swiss * C57BL/6 * DBA/2* FVB/N

Additional - Hba^tm1Paz related

Additional - Hbb^tm1Tow related