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 Mutant Stock; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Species laboratory mouse   Donating Investigator Anna R. Migliaccio,   Istituto Superiore Sanità

Description
Mice that are homozygous for the targeted mutation are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. Reduced levels of gene product (mRNA) is detected by RT-PCR analysis. Mutant mice are thrombocytopenic and anemic at birth. Adult mutant mice have enlarged spleens and exhibit thrombocytopenia due to arrested megakaryocyte maturation which results in increased megakaryocytes in spleen and bone marrow. Platelet number in adult mutant mice is only 10% of wildtype. Erythroblast and mast cell differentiation is defective as indicated by increased apoptotic rates and accumulation of progenitors. Mutant mice display an enhanced response and recovery to experimentally induced acute and chronic erythropoiesis stimulation. At 15 months of age, homozygous female and heterozygous male mutant mice begin to develop idiopathic myelofibrosis-like symptoms including: anemia, tear-drop poikilocytes, progenitor cells in the blood, collagen fibers and osteogenesis in the bone marrow, collagen fibers in the spleen and hematopoietic foci in the liver. This mutant mouse strain may be useful in studies of hematopoiesis.

Development
A targeting vector containing a loxP site flanked neomycin resistance gene driven by the mouse phosphoglycerate kinase promoter and a herpes simplex virus thymidine kinase gene was used to disrupt the I-testes (IT) promoter and Dnase I-hypersensitive (HS) regions of the targeted gene. The construct was electroporated into 129S4/SvJae derived J1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts.

Control Information

	Control
	Wild-type from the colony
Considerations for Choosing Controls

Related Strains

Strains carrying other alleles of Gata1

016911	B6.Cg-Tg(Gata1-CR1)1Rwf/J
005653	C.Cg-Gata1tm6Sho/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

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

Gata1^tm2Sho/Gata1⁺

        involves: 129S4/SvJae * C57BL/6

• hematopoietic system phenotype
• abnormal megakaryocyte progenitor cell morphology
  • proliferation of megakaryocyte progenitors is greatly enhanced in fetal livers, presumably because of mosaicism resulting from random X inactivation   (MGI Ref ID J:41605)
• • abnormal megakaryocyte differentiation   (MGI Ref ID J:41605)
  • increased megakaryocyte cell number
    • large increase in megakaryocytes in hematopoietic tissues, presumably because of mosaicism resulting from random X inactivation   (MGI Ref ID J:41605)
    • excess of abnormal megakaryocytes in the yolk sac and early fetal liver   (MGI Ref ID J:41605)
    • however, normal numbers of platelets   (MGI Ref ID J:41605)
• cellular phenotype
• abnormal megakaryocyte differentiation   (MGI Ref ID J:41605)

Gata1^tm2Sho/Gata1^tm2Sho

        involves: 129S4/SvJae

• skeleton phenotype
• abnormal bone ossification
  • bone formation is increased 2.7-fold compared to in wild-type mice   (MGI Ref ID J:111270)
• increased compact bone volume
  • at 5 to 9 months of age, the cortical bone is increased 2- to 3-fold compared to in wild-type mice   (MGI Ref ID J:111270)
• increased osteoblast cell number
  • the number of osteoblasts is increased by greater than 3-fold compared to in wild-type mice and is accompanied by a proportional increase in osteoclasts   (MGI Ref ID J:111270)
  • osteoblast proliferation is increased up to 6-fold when cultured with megakaryocytes compared to in wild-type mice   (MGI Ref ID J:111270)
• increased osteoclast cell number
  • the number of osteoclasts is increased by greater than 3-fold compared to in wild-type mice and is accompanied by a proportional increase in osteoblasts   (MGI Ref ID J:111270)
• increased trabecular bone volume
  • trabecular bone volume for the entire medullary canal is increased 150-fold compared to in wild-type mice   (MGI Ref ID J:111270)
  • at 5 to 9 months of age, the trabecular bone is increased 2- to 3-fold compared to in wild-type mice   (MGI Ref ID J:111270)
  • at 5 months, the diaphyseal shafts are occluded with bone unlike in wild-type mice   (MGI Ref ID J:111270)
• hematopoietic system phenotype
• increased osteoclast cell number
  • the number of osteoclasts is increased by greater than 3-fold compared to in wild-type mice and is accompanied by a proportional increase in osteoblasts   (MGI Ref ID J:111270)
• immune system phenotype
• increased osteoclast cell number
  • the number of osteoclasts is increased by greater than 3-fold compared to in wild-type mice and is accompanied by a proportional increase in osteoblasts   (MGI Ref ID J:111270)

Gata1^tm2Sho/Y

        involves: 129S4/SvJae * C57BL/6

• mortality/aging
• decreased survivor rate
  • 5% of males survive fetal anemia into adult life   (MGI Ref ID J:41605)
• hematopoietic system phenotype
• abnormal megakaryocyte progenitor cell morphology
  • proliferation of megakaryocyte progenitors is greatly enhanced in fetal livers   (MGI Ref ID J:41605)
• • abnormal megakaryocyte morphology
    • megakaryocytes are smaller than normal, have scant cytoplasm and condensed nuclei   (MGI Ref ID J:41605)
  • • abnormal megakaryocyte differentiation
      • maturation of megakaryocytes is arrested   (MGI Ref ID J:41605)
    • increased mean platelet volume   (MGI Ref ID J:41605)
    • increased megakaryocyte cell number
      • 100-fold increase in megakaryocytes in the spleen and bone marrow   (MGI Ref ID J:41605)
      • excess of abnormal megakaryocytes in the yolk sac and early fetal liver   (MGI Ref ID J:41605)
• anemia   (MGI Ref ID J:41605)
• decreased platelet cell number
  • platelet numbers are reduced to about 15% of normal   (MGI Ref ID J:41605)
• cellular phenotype
• abnormal megakaryocyte differentiation
  • maturation of megakaryocytes is arrested   (MGI Ref ID J:41605)

Gata1^tm2Sho/Y

        involves: 129S4/SvJae * C57BL/6 * CD-1

• hematopoietic system phenotype
• abnormal common myeloid progenitor cell morphology
  • spleen and marrow contains increased numbers of megakaryocytic and bipotent (erythroid/megakaryocytic) precursors   (MGI Ref ID J:78540)
• abnormal erythroid progenitor cell morphology   (MGI Ref ID J:78540)
• • decreased erythroid progenitor cell number
    • overall erythroid precursor cell content in the marrow is lower than in wild-type   (MGI Ref ID J:78540)
  • increased erythroid progenitor cell number
    • marrow and spleen contain a higher frequency of burst-forming units-erythroid (BFU-E)- and colony-forming units-erythroid (CFU-E) derived colonies   (MGI Ref ID J:78540)
    • spleen contains 7-20-fold higher numbers of erythroid precursors and bipotent (erythroid/megakaryocytic) precursors   (MGI Ref ID J:78540)
    • phenylhydrazine (PHZ) treated mutants exhibit an increase in CFU-E   (MGI Ref ID J:78540)
    • erythropoietin (EPO) treated mutants exhibit an increase in both early (BFU-E) and late (CFU-E) progenitor cells in the marrow and spleen   (MGI Ref ID J:78540)
• abnormal hematocrit
  • mutants exhibit an accelerated hematocrit response to both acute (PHZ treatment) and chronic (EPO administration) erythroid stimulation which lasts longer than in wild-type   (MGI Ref ID J:78540)
• abnormal platelet morphology
  • platelets appear abnormal and bigger than normal platelets   (MGI Ref ID J:78540)
• abnormal spleen red pulp morphology
  • the interfollicular space of the red pulp is filled with abnormally large and dysplastic megakaryocytes   (MGI Ref ID J:78540)
  • red pulp and subcapsulary space are filled with lymphocyte-sized cells resembling immature erythroid cells   (MGI Ref ID J:78540)
• decreased bone marrow cell number
  • bone marrow contains 3 times fewer cells than wild-type   (MGI Ref ID J:78540)
• decreased platelet cell number
  • 10-fold decrease in platelet numbers   (MGI Ref ID J:78540)
  • mutants are thrombocytopenic in response to phenylhydrazine (PHZ)-induced anemia or erythropoietin (EPO)-iduced polycythemia but have normal hematocrit levels   (MGI Ref ID J:78540)
• enlarged spleen
  • spleens are 2.5-fold larger   (MGI Ref ID J:78540)
  • spleens of PHZ-and EPO-treated mutants are bigger and contain more cells than treated controls   (MGI Ref ID J:78540)
• extramedullary hematopoiesis
  • transition of the major hematopoietic site from the marrow to the spleen   (MGI Ref ID J:78540)
• increased splenocyte number
  • spleen contains 3 times more cells than wild-type   (MGI Ref ID J:78540)
• homeostasis/metabolism phenotype
• abnormal physiological response to xenobiotic
  • mutants recover 2 days faster from the PHZ-induced anemia than controls   (MGI Ref ID J:78540)
• immune system phenotype
• abnormal spleen red pulp morphology
  • the interfollicular space of the red pulp is filled with abnormally large and dysplastic megakaryocytes   (MGI Ref ID J:78540)
  • red pulp and subcapsulary space are filled with lymphocyte-sized cells resembling immature erythroid cells   (MGI Ref ID J:78540)
• enlarged spleen
  • spleens are 2.5-fold larger   (MGI Ref ID J:78540)
  • spleens of PHZ-and EPO-treated mutants are bigger and contain more cells than treated controls   (MGI Ref ID J:78540)
• increased splenocyte number
  • spleen contains 3 times more cells than wild-type   (MGI Ref ID J:78540)
• skeleton phenotype
• abnormal bone marrow morphology
  • bone marrow contains larger-than-normal red cells and apoptotic cells   (MGI Ref ID J:78540)

View Research Applications

Research Applications

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

Internal/Organ Research
Skeleton
      Bone

Gata1^tm2Sho related

Hematological Research
Anemia, Iron Deficiency and Transport Defects
Hematopoietic Defects
Mast Cell Deficiency
Platelet Defects
      thrombocytopenia

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		Gata1tm2Sho
Allele Name		targeted mutation 2, Stuart Orkin
Allele Type		Targeted (knock-out)
Common Name(s)		GATA-1low; neo deltaHS; neodeltaHS;
Mutation Made By		Dr. Stuart Orkin,   Harvard Medical School
Strain of Origin		129S4/SvJae
ES Cell Line Name		J1
ES Cell Line Strain		129S4/SvJae
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 loxP-flanked neomycin selection cassette replaced the "IT" and DNAseI hypersensitive region of the promoter. RT-PCR experiments demonstrated that this mutation resulted in the loss of expression in megakaryocytes and fetal liver but not in erythroid cells. [MGI Ref ID J:41605]

Genotyping

Genotyping Information

Genotyping Protocols

Gata1^tm2sho, Standard PCR

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Vannucchi AM; Bianchi L; Cellai C; Paoletti F; Carrai V; Calzolari A; Centurione L; Lorenzini R; Carta C; Alfani E; Sanchez M; Migliaccio G; Migliaccio AR. 2001. Accentuated response to phenylhydrazine and erythropoietin in mice genetically impaired for their GATA-1 expression (GATA-1(low) mice). Blood 97(10):3040-50. [PubMed: 11342429]  [MGI Ref ID J:78540]

Additional References

Migliaccio AR; Rana RA; Sanchez M; Lorenzini R; Centurione L; Bianchi L; Vannucchi AM; Migliaccio G; Orkin SH. 2003. GATA-1 as a regulator of mast cell differentiation revealed by the phenotype of the GATA-1low mouse mutant. J Exp Med 197(3):281-96. [PubMed: 12566412]  [MGI Ref ID J:81780]

Vannucchi AM; Bianchi L; Cellai C; Paoletti F; Rana RA; Lorenzini R; Migliaccio G; Migliaccio AR. 2002. Development of myelofibrosis in mice genetically impaired for GATA-1 expression (GATA-1(low) mice). Blood 100(4):1123-32. [PubMed: 12149188]  [MGI Ref ID J:78348]

Gata1^tm2Sho related

Centurione L; Di Baldassarre A; Zingariello M; Bosco D; Gatta V; Rana RA; Langella V; Di Virgilio A; Vannucchi AM; Migliaccio AR. 2004. Increased and pathologic emperipolesis of neutrophils within megakaryocytes associated with marrow fibrosis in GATA-1(low) mice. Blood 104(12):3573-80. [PubMed: 15292068]  [MGI Ref ID J:94831]

Elagib KE; Mihaylov IS; Delehanty LL; Bullock GC; Ouma KD; Caronia JF; Gonias SL; Goldfarb AN. 2008. Cross-talk of GATA-1 and P-TEFb in megakaryocyte differentiation. Blood 112(13):4884-94. [PubMed: 18780834]  [MGI Ref ID J:143622]

Garimella R; Kacena MA; Tague SE; Wang J; Horowitz MC; Anderson HC. 2007. Expression of bone morphogenetic proteins and their receptors in the bone marrow megakaryocytes of GATA-1(low) mice: a possible role in osteosclerosis. J Histochem Cytochem 55(7):745-52. [PubMed: 17371937]  [MGI Ref ID J:123113]

Gurbuxani S; Vyas P; Crispino JD. 2004. Recent insights into the mechanisms of myeloid leukemogenesis in Down syndrome. Blood 103(2):399-406. [PubMed: 14512321]  [MGI Ref ID J:87699]

Kacena MA; Shivdasani RA; Wilson K; Xi Y; Troiano N; Nazarian A; Gundberg CM; Bouxsein ML; Lorenzo JA; Horowitz MC. 2004. Megakaryocyte-osteoblast interaction revealed in mice deficient in transcription factors GATA-1 and NF-E2. J Bone Miner Res 19(4):652-60. [PubMed: 15005853]  [MGI Ref ID J:111270]

Kaneko H; Kobayashi E; Yamamoto M; Shimizu R. 2012. N- and C-terminal transactivation domains of GATA1 protein coordinate hematopoietic program. J Biol Chem 287(25):21439-49. [PubMed: 22556427]  [MGI Ref ID J:186500]

Martelli F; Ghinassi B; Panetta B; Alfani E; Gatta V; Pancrazzi A; Bogani C; Vannucchi AM; Paoletti F; Migliaccio G; Migliaccio AR. 2005. Variegation of the phenotype induced by the Gata1low mutation in mice of different genetic backgrounds. Blood 106(13):4102-13. [PubMed: 16109774]  [MGI Ref ID J:124063]

McDevitt MA; Shivdasani RA; Fujiwara Y; Yang H; Orkin SH. 1997. A 'knockdown' mutation created by cis-element gene targeting reveals the dependence of erythroid cell maturation on the level of transcription factor GATA-1. Proc Natl Acad Sci U S A 94(13):6781-5. [PubMed: 9192642]  [MGI Ref ID J:75840]

Migliaccio AR; Martelli F; Verrucci M; Migliaccio G; Vannucchi AM; Ni H; Xu M; Jiang Y; Nakamoto B; Papayannopoulou T; Hoffman R. 2008. Altered SDF-1/CXCR4 axis in patients with primary myelofibrosis and in the Gata1 low mouse model of the disease. Exp Hematol 36(2):158-71. [PubMed: 18206727]  [MGI Ref ID J:132618]

Migliaccio AR; Martelli F; Verrucci M; Sanchez M; Valeri M; Migliaccio G; Vannucchi AM; Zingariello M; Di Baldassarre A; Ghinassi B; Rana RA; van Hensbergen Y; Fibbe WE. 2009. Gata1 expression driven by the alternative HS2 enhancer in the spleen rescues the hematopoietic failure induced by the hypomorphic Gata1low mutation. Blood 114(10):2107-20. [PubMed: 19571316]  [MGI Ref ID J:152244]

Migliaccio AR; Rana RA; Sanchez M; Lorenzini R; Centurione L; Bianchi L; Vannucchi AM; Migliaccio G; Orkin SH. 2003. GATA-1 as a regulator of mast cell differentiation revealed by the phenotype of the GATA-1low mouse mutant. J Exp Med 197(3):281-96. [PubMed: 12566412]  [MGI Ref ID J:81780]

Sanchez M; Weissman IL; Pallavicini M; Valeri M; Guglielmelli P; Vannucchi AM; Migliaccio G; Migliaccio AR. 2006. Differential amplification of murine bipotent megakaryocytic/erythroid progenitor and precursor cells during recovery from acute and chronic erythroid stress. Stem Cells 24(2):337-48. [PubMed: 16144876]  [MGI Ref ID J:129225]

Shivdasani RA; Fujiwara Y; McDevitt MA; Orkin SH. 1997. A lineage-selective knockout establishes the critical role of transcription factor GATA-1 in megakaryocyte growth and platelet development. EMBO J 16(13):3965-73. [PubMed: 9233806]  [MGI Ref ID J:41605]

Vannucchi AM; Bianchi L; Cellai C; Paoletti F; Rana RA; Lorenzini R; Migliaccio G; Migliaccio AR. 2002. Development of myelofibrosis in mice genetically impaired for GATA-1 expression (GATA-1(low) mice). Blood 100(4):1123-32. [PubMed: 12149188]  [MGI Ref ID J:78348]

Vannucchi AM; Bianchi L; Paoletti F; Pancrazzi A; Torre E; Nishikawa M; Zingariello M; Di Baldassarre A; Rana RA; Lorenzini R; Alfani E; Migliaccio G; Migliaccio AR. 2005. A pathobiologic pathway linking thrombopoietin, GATA-1, and TGF-beta1 in the development of myelofibrosis. Blood 105(9):3493-501. [PubMed: 15665119]  [MGI Ref ID J:98976]

Vyas P; Ault K; Jackson CW; Orkin SH; Shivdasani RA. 1999. Consequences of GATA-1 deficiency in megakaryocytes and platelets. Blood 93(9):2867-75. [PubMed: 10216081]  [MGI Ref ID J:54571]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200.

Colony Maintenance

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
	Wild-type from the colony
Considerations for Choosing Controls
Control Pricing Information for Genetically Engineered Mutant Strains.

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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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