Description

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. Mating System Homozygote x Hemizygote         (Female x Male)   31-MAR-06 Species laboratory mouse Generation N8+F14 (30-NOV-12) Generation Definitions   Donating Investigator Dr. Stuart Orkin,   Harvard Medical School

Description
Homozygous females and hemizygous males for the targeted mutation are viable, fertile, and normal in size. This mutation results in the complete ablation of the eosinophil lineage, even under conditions that normally stimulate eosinophil development, without affecting the development of other GATA-1 dependent lineages (erythroid, megakaryocytic, and mast cells). Expression of the endogenous gene is observed in erythroid and bone marrow cells. This mutant may be useful for in vivo studies of eosinophil function and eosinophil-related pathologies, including asthma and pulmonary physiology.

Development
A targeting vector was designed to replace the double GATA-site 21 bp upstream of the first hematopoietic exon of the X-linked endogenous gene. This vector, containing a loxP-flanked phosphoglycerate kinase promoter driven neomycin resistance gene (PGK-neo), was electroporated into 129S1/Sv derived CJ-7 embryonic stem (ES) cells. Correctly targeted ES cells were then transiently transfected with a cre recombinase vector to remove the PGK-neo resulting in a mutant allele where the double GATA-site is replaced with a single loxP site. These cells were injected into C57BL/6 blastocysts and the resulting chimeric males were backcrossed to C57BL/6 females. Resultant heterozygotes were backcrossed to BALB/c for eight generations before being made homozygous/hemizygous.

Control Information

	Control
	000651 BALB/cJ
Considerations for Choosing Controls

Related Strains

Strains carrying other alleles of Gata1

016911	B6.Cg-Tg(Gata1-CR1)1Rwf/J
004655	STOCK Gata1tm2Sho/J

View Strains carrying other alleles of Gata1     (2 strains)

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms provided by MGI

- Potential model based on gene homology relationships. Phenotypic similarity to the human disease has not been tested. Anemia, X-Linked, with or without Neutropenia and/or Platelet Abnormalities;   (GATA1) Down Syndrome   (GATA1) Thrombocytopenia with Beta-Thalassemia, X-Linked; XLTT   (GATA1) Thrombocytopenia, X-Linked, with or without Dyserythropoietic Anemia;   (GATA1)

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI

      assigned by genotype

Gata1^tm6Sho/Gata1^tm6Sho

        C.129S1-Gata1^tm6Sho

• immune system phenotype
• autoimmune response
  • mutants exhibit impaired epidermal and dermal thickening and collagen deposition in OVA-sensitized skin (to induce allergic skin inflammation) compared to wild-type mice   (MGI Ref ID J:182213)
  • eosinophils are not detectable in skin of EC-sensitized mutants with OVA, however dermal infiltration by CD4+ cells is similar to wild-type mice and systemic immune response to EC sensitization with OVA is comparable to wild-type controls   (MGI Ref ID J:182213)
• integument phenotype
• abnormal skin physiology
  • mutants exhibit impaired epidermal and dermal thickening and collagen deposition in OVA-sensitized skin (to induce allergic skin inflammation) compared to wild-type mice   (MGI Ref ID J:182213)

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

Gata1^tm6Sho/Gata1^tm6Sho

        involves: 129S1/Sv

• hematopoietic system phenotype
• *normal* hematopoietic system phenotype
  • all other hematopoietic lineages are normal   (MGI Ref ID J:88711)
  • mutants are viable, fertile and have no gross abnormalities   (MGI Ref ID J:88711)
• • decreased eosinophil cell number
    • eosinophils are absent   (MGI Ref ID J:88711)
• immune system phenotype
• decreased eosinophil cell number
  • eosinophils are absent   (MGI Ref ID J:88711)

Gata1^tm6Sho/Gata1^tm6Sho

        involves: 129S1/Sv * BALB/c

• respiratory system phenotype
• *normal* respiratory system phenotype
  • methacholine induced airway hypersensitivity is unaffected   (MGI Ref ID J:92849)
• • abnormal bronchiole morphology
    • reduced extracellular matrix deposition in bronchioles after allergen challenge   (MGI Ref ID J:92849)
    • also in perivascular regions   (MGI Ref ID J:92849)
  • abnormal respiratory system physiology
    • reduced mucus production after Aspergillus fumigatus exposure   (MGI Ref ID J:92849)
    • airway smooth muscle proliferation does not occur in response to allergen   (MGI Ref ID J:92849)
• hematopoietic system phenotype
• abnormal leukocyte cell number
  • impaired recruitment into bronchoalveolar lavage fluid generally   (MGI Ref ID J:115273)
• • decreased eosinophil cell number
    • eosinophils are absent in bronchoalveolar lavage fluid after Aspergillus fumigatus exposure   (MGI Ref ID J:115273)
  • decreased lymphocyte cell number
    • 50% lymphocyte reduction in bronchoalveolar lavage fluid after Aspergillus fumigatus exposure   (MGI Ref ID J:115273)
  • increased neutrophil cell number
    • three fold increase in airway neutrophilia after Aspergillus fumigatus exposure   (MGI Ref ID J:115273)
• immune system phenotype
• abnormal leukocyte cell number
  • impaired recruitment into bronchoalveolar lavage fluid generally   (MGI Ref ID J:115273)
• • decreased eosinophil cell number
    • eosinophils are absent in bronchoalveolar lavage fluid after Aspergillus fumigatus exposure   (MGI Ref ID J:115273)
  • decreased lymphocyte cell number
    • 50% lymphocyte reduction in bronchoalveolar lavage fluid after Aspergillus fumigatus exposure   (MGI Ref ID J:115273)
  • increased neutrophil cell number
    • three fold increase in airway neutrophilia after Aspergillus fumigatus exposure   (MGI Ref ID J:115273)
• decreased circulating interleukin-13 level
  • after Aspergillus fumigatus exposure   (MGI Ref ID J:115273)
• decreased circulating interleukin-4 level
  • after Aspergillus fumigatus exposure   (MGI Ref ID J:115273)
• homeostasis/metabolism phenotype
• abnormal hemostasis
  • more modest increase in coagulation components after allergen stimulation than seen in controls   (MGI Ref ID J:115273)
• decreased circulating interleukin-13 level
  • after Aspergillus fumigatus exposure   (MGI Ref ID J:115273)
• decreased circulating interleukin-4 level
  • after Aspergillus fumigatus exposure   (MGI Ref ID J:115273)

Gata1^tm6Sho/Y

        involves: 129S1/Sv

• hematopoietic system phenotype
• *normal* hematopoietic system phenotype
  • mast cell production in the bone marrow is normal   (MGI Ref ID J:88711)
• • decreased eosinophil cell number
    • eosinophils are absent   (MGI Ref ID J:88711)
  • decreased erythrocyte cell number
    • erythrocyte number is reduced by 27% in males   (MGI Ref ID J:88711)
  • decreased hematocrit
    • hemoglobin level is reduced in proportion with the reduction in erythrocyte number   (MGI Ref ID J:88711)
  • enlarged spleen
    • modest splenomegaly is seen in males   (MGI Ref ID J:88711)
• immune system phenotype
• decreased eosinophil cell number
  • eosinophils are absent   (MGI Ref ID J:88711)
• enlarged spleen
  • modest splenomegaly is seen in males   (MGI Ref ID J:88711)

View Research Applications

Research Applications

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

Developmental Biology Research
Lymphoid Tissue Defects
      hematopoietic defects

Hematological Research
Hematopoietic Defects

Immunology, Inflammation and Autoimmunity Research
Immunodeficiency
      Asthma
Inflammation
      Asthma
Lymphoid Tissue Defects
      hematopoietic development

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		Gata1tm6Sho
Allele Name		targeted mutation 6, Stuart Orkin
Allele Type		Targeted (knock-out)
Common Name(s)		Eos-; Gata1tm5Sho; deltadbl GATA; deltadblGATA;
Mutation Made By		Dr. Stuart Orkin,   Harvard Medical School
Strain of Origin		129S1/Sv-Oca2<+> Tyr<+> Kitl<+>
ES Cell Line Name		CJ7
ES Cell Line Strain		129S1/Sv-Oca2<+> Tyr<+> Kitl<+>
Gene Symbol and Name		Gata1, GATA binding protein 1
Chromosome		X
Gene Common Name(s)		ERYF1; GATA-1; GF-1; GF1; Gata-1; Gf-1; NFE1; XLANP; XLTDA; XLTT; globin factor 1;
Molecular Note		A high-affinity, palindromic "double" GATA protein binding site in the Gata1 promoter presumed to mediate positive Gata1 autoregulation was replaced by a floxed Pgk-neo cassette; transient Cre recombinase expression in ES cells left a single loxP site flanked by two Not1 sites. The 21-bp deleted segment comprised nucleotides -691 through -671 upstream of the last nucleotide of the first hematopoietically expressed exon of Gata1. [MGI Ref ID J:88711]

Genotyping

Genotyping Information

Genotyping Protocols

Gata1^tm6Sho, Standard PCR

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Yu C; Cantor AB; Yang H; Browne C; Wells RA; Fujiwara Y; Orkin SH. 2002. Targeted deletion of a high-affinity GATA-binding site in the GATA-1 promoter leads to selective loss of the eosinophil lineage in vivo. J Exp Med 195(11):1387-95. [PubMed: 12045237]  [MGI Ref ID J:88711]

Additional References

Gata1^tm6Sho related

Castilow EM; Legge KL; Varga SM. 2008. Cutting edge: Eosinophils do not contribute to respiratory syncytial virus vaccine-enhanced disease. J Immunol 181(10):6692-6. [PubMed: 18981084]  [MGI Ref ID J:140954]

Cho KA; Suh JW; Sohn JH; Park JW; Lee H; Kang JL; Woo SY; Cho YJ. 2012. IL-33 induces Th17-mediated airway inflammation via mast cells in ovalbumin-challenged mice. Am J Physiol Lung Cell Mol Physiol 302(4):L429-40. [PubMed: 22180658]  [MGI Ref ID J:183444]

Dyer KD; Czapiga M; Foster B; Foster PS; Kang EM; Lappas CM; Moser JM; Naumann N; Percopo CM; Siegel SJ; Swartz JM; Ting-De Ravin S; Rosenberg HF. 2007. Eosinophils from lineage-ablated Delta dblGATA bone marrow progenitors: the dblGATA enhancer in the promoter of GATA-1 is not essential for differentiation ex vivo. J Immunol 179(3):1693-9. [PubMed: 17641035]  [MGI Ref ID J:149946]

Fabre V; Beiting DP; Bliss SK; Gebreselassie NG; Gagliardo LF; Lee NA; Lee JJ; Appleton JA. 2009. Eosinophil deficiency compromises parasite survival in chronic nematode infection. J Immunol 182(3):1577-83. [PubMed: 19155506]  [MGI Ref ID J:144323]

Fu W; Ergun A; Lu T; Hill JA; Haxhinasto S; Fassett MS; Gazit R; Adoro S; Glimcher L; Chan S; Kastner P; Rossi D; Collins JJ; Mathis D; Benoist C. 2012. A multiply redundant genetic switch 'locks in' the transcriptional signature of regulatory T cells. Nat Immunol 13(10):972-80. [PubMed: 22961053]  [MGI Ref ID J:187667]

Fulkerson PC; Fischetti CA; McBride ML; Hassman LM; Hogan SP; Rothenberg ME. 2006. A central regulatory role for eosinophils and the eotaxin/CCR3 axis in chronic experimental allergic airway inflammation. Proc Natl Acad Sci U S A 103(44):16418-23. [PubMed: 17060636]  [MGI Ref ID J:115273]

Fulkerson PC; Fischetti CA; Rothenberg ME. 2006. Eosinophils and CCR3 regulate interleukin-13 transgene-induced pulmonary remodeling. Am J Pathol 169(6):2117-26. [PubMed: 17148674]  [MGI Ref ID J:116219]

Gebreselassie NG; Moorhead AR; Fabre V; Gagliardo LF; Lee NA; Lee JJ; Appleton JA. 2012. Eosinophils preserve parasitic nematode larvae by regulating local immunity. J Immunol 188(1):417-25. [PubMed: 22131328]  [MGI Ref ID J:180814]

Humbles AA; Lloyd CM; McMillan SJ; Friend DS; Xanthou G; McKenna EE; Ghiran S; Gerard NP; Yu C; Orkin SH; Gerard C. 2004. A critical role for eosinophils in allergic airways remodeling. Science 305(5691):1776-9. [PubMed: 15375268]  [MGI Ref ID J:92849]

Jessup HK; Brewer AW; Omori M; Rickel EA; Budelsky AL; Yoon BR; Ziegler SF; Comeau MR. 2008. Intradermal administration of thymic stromal lymphopoietin induces a T cell- and eosinophil-dependent systemic Th2 inflammatory response. J Immunol 181(6):4311-9. [PubMed: 18768889]  [MGI Ref ID J:139079]

Kim HJ; Alonzo ES; Dorothee G; Pollard JW; Sant'Angelo DB. 2010. Selective depletion of eosinophils or neutrophils in mice impacts the efficiency of apoptotic cell clearance in the thymus. PLoS One 5(7):e11439. [PubMed: 20625428]  [MGI Ref ID J:163125]

McKee AS; Munks MW; MacLeod MK; Fleenor CJ; Van Rooijen N; Kappler JW; Marrack P. 2009. Alum induces innate immune responses through macrophage and mast cell sensors, but these sensors are not required for alum to act as an adjuvant for specific immunity. J Immunol 183(7):4403-14. [PubMed: 19734227]  [MGI Ref ID J:152787]

Mishra A; Wang M; Pemmaraju VR; Collins MH; Fulkerson PC; Abonia JP; Blanchard C; Putnam PE; Rothenberg ME. 2008. Esophageal remodeling develops as a consequence of tissue specific IL-5-induced eosinophilia. Gastroenterology 134(1):204-14. [PubMed: 18166354]  [MGI Ref ID J:135588]

Munitz A; McBride ML; Bernstein JS; Rothenberg ME. 2008. A dual activation and inhibition role for the paired immunoglobulin-like receptor B in eosinophils. Blood 111(12):5694-703. [PubMed: 18316626]  [MGI Ref ID J:136634]

Oyoshi MK; He R; Kanaoka Y; Elkhal A; Kawamoto S; Lewis CN; Austen KF; Geha RS. 2012. Eosinophil-derived leukotriene C4 signals via type 2 cysteinyl leukotriene receptor to promote skin fibrosis in a mouse model of atopic dermatitis. Proc Natl Acad Sci U S A 109(13):4992-7. [PubMed: 22416124]  [MGI Ref ID J:182213]

Percopo CM; Qiu Z; Phipps S; Foster PS; Domachowske JB; Rosenberg HF. 2009. Pulmonary eosinophils and their role in immunopathologic responses to formalin-inactivated pneumonia virus of mice. J Immunol 183(1):604-12. [PubMed: 19542471]  [MGI Ref ID J:149965]

Piehler D; Stenzel W; Grahnert A; Held J; Richter L; Kohler G; Richter T; Eschke M; Alber G; Muller U. 2011. Eosinophils Contribute to IL-4 Production and Shape the T-Helper Cytokine Profile and Inflammatory Response in Pulmonary Cryptococcosis. Am J Pathol 179(2):733-44. [PubMed: 21699881]  [MGI Ref ID J:174409]

Price AE; Liang HE; Sullivan BM; Reinhardt RL; Eisley CJ; Erle DJ; Locksley RM. 2010. Systemically dispersed innate IL-13-expressing cells in type 2 immunity. Proc Natl Acad Sci U S A 107(25):11489-94. [PubMed: 20534524]  [MGI Ref ID J:161387]

Rankin AL; Mumm JB; Murphy E; Turner S; Yu N; McClanahan TK; Bourne PA; Pierce RH; Kastelein R; Pflanz S. 2010. IL-33 induces IL-13-dependent cutaneous fibrosis. J Immunol 184(3):1526-35. [PubMed: 20042577]  [MGI Ref ID J:159528]

Richter K; Hausmann J; Staeheli P. 2009. Interferon-gamma prevents death of bystander neurons during CD8 T cell responses in the brain. Am J Pathol 174(5):1799-807. [PubMed: 19359516]  [MGI Ref ID J:147967]

Siegle JS; Hansbro N; Herbert C; Yang M; Foster PS; Kumar RK. 2006. Airway hyperreactivity in exacerbation of chronic asthma is independent of eosinophilic inflammation. Am J Respir Cell Mol Biol 35(5):565-70. [PubMed: 16794258]  [MGI Ref ID J:126888]

Simson L; Ellyard JI; Dent LA; Matthaei KI; Rothenberg ME; Foster PS; Smyth MJ; Parish CR. 2007. Regulation of carcinogenesis by IL-5 and CCL11: a potential role for eosinophils in tumor immune surveillance. J Immunol 178(7):4222-9. [PubMed: 17371978]  [MGI Ref ID J:122672]

Swartz JM; Dyer KD; Cheever AW; Ramalingam T; Pesnicak L; Domachowske JB; Lee JJ; Lee NA; Foster PS; Wynn TA; Rosenberg HF. 2006. Schistosoma mansoni infection in eosinophil lineage-ablated mice. Blood 108(7):2420-7. [PubMed: 16772607]  [MGI Ref ID J:139471]

Tsai M; Chen CC; Mukai K; Song CH; Thompson LJ; Ziegler SF; Tam SY; Galli SJ. 2010. Thymic stromal lymphopoietin contributes to myeloid hyperplasia and increased immunoglobulins, but not epidermal hyperplasia, in RabGEF1-deficient mice. Am J Pathol 177(5):2411-20. [PubMed: 20829437]  [MGI Ref ID J:166267]

Vieira AT; Fagundes CT; Alessandri AL; Castor MG; Guabiraba R; Borges VO; Silveira KD; Vieira EL; Goncalves JL; Silva TA; Deruaz M; Proudfoot AE; Sousa LP; Teixeira MM. 2009. Treatment with a novel chemokine-binding protein or eosinophil lineage-ablation protects mice from experimental colitis. Am J Pathol 175(6):2382-91. [PubMed: 19893035]  [MGI Ref ID J:155325]

Voehringer D; Reese TA; Huang X; Shinkai K; Locksley RM. 2006. Type 2 immunity is controlled by IL-4/IL-13 expression in hematopoietic non-eosinophil cells of the innate immune system. J Exp Med 203(6):1435-46. [PubMed: 16702603]  [MGI Ref ID J:124383]

Voehringer D; van Rooijen N; Locksley RM. 2007. Eosinophils develop in distinct stages and are recruited to peripheral sites by alternatively activated macrophages. J Leukoc Biol 81(6):1434-44. [PubMed: 17339609]  [MGI Ref ID J:122340]

Walsh ER; Sahu N; Kearley J; Benjamin E; Kang BH; Humbles A; August A. 2008. Strain-specific requirement for eosinophils in the recruitment of T cells to the lung during the development of allergic asthma. J Exp Med 205(6):1285-92. [PubMed: 18490489]  [MGI Ref ID J:137076]

Walsh ER; Thakar J; Stokes K; Huang F; Albert R; August A. 2011. Computational and Experimental Analysis Reveals a Requirement for Eosinophil-Derived IL-13 for the Development of Allergic Airway Responses in C57BL/6 Mice. J Immunol 186(5):2936-49. [PubMed: 21289305]  [MGI Ref ID J:169374]

Wu D; Molofsky AB; Liang HE; Ricardo-Gonzalez RR; Jouihan HA; Bando JK; Chawla A; Locksley RM. 2011. Eosinophils sustain adipose alternatively activated macrophages associated with glucose homeostasis. Science 332(6026):243-7. [PubMed: 21436399]  [MGI Ref ID J:170307]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           AX12

Colony Maintenance

Breeding & Husbandry	When maintaining a live colony, this colony is maintained as homozygotes.
Mating System	Homozygote x Hemizygote         (Female x Male)   31-MAR-06
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
	000651 BALB/cJ
Considerations for Choosing Controls
Control Pricing Information for Genetically Engineered Mutant Strains.

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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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