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Type Mutant Stock; Targeted Mutation; Additional information on Genetically Engineered Mutant Mice. Species laboratory mouse Donating Investigator Anna 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 | ||
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| Wild-type from the colony | ||
| Considerations for Choosing Controls | ||
Strains carrying other alleles of Gata1
005653 C.Cg-Gata1tm6Sho/J View Strains carrying other alleles of Gata1 (1 strain)
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.
Gata1tm2Sho/Gata1tm2Sho
involves: 129S4/SvJae
- skeleton phenotype
- abnormal bone ossification (MGI Ref ID J:111270)
- bone formation is increased 2.7-fold compared to in wild-type mice
- abnormal bone structure (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
- at 5 months, the diaphyseal shafts are occluded with bone unlike in wild-type mice
- abnormal bone marrow cavity morphology (MGI Ref ID J:111270)
- trabecular bone volume for the entire medullary canal is increased 150-fold compared to in wild-type mice
- abnormal cortical bone morphology (MGI Ref ID J:111270)
- at 5 to 9 months of age, the cortical bone is increased 2- to 3-fold compared to in wild-type mice
- increased osteoblast cell number (MGI Ref ID J:111270)
- 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
- osteoblast proliferation is increased up to 6-fold when cultured with megakaryocytes compared to in wild-type mice
- increased osteoclast cell number (MGI Ref ID J:111270)
- 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
- hematopoietic system phenotype
- increased osteoclast cell number (MGI Ref ID J:111270)
- 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
- immune system phenotype
- increased osteoclast cell number (MGI Ref ID J:111270)
- 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
View Research Applications
Research Applications
This mouse can be used to support research in many areas including:Gata1tm2Sho related
Hematological Research
Anemia, Iron Deficiency and Transport Defects
Hematopoietic Defects
Mast Cell Deficiency
Platelet Defects (thrombocytopenia)
| 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 | 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; GF-1; GF1; Gata-1; Gf-1; NFE1; 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. [MGI Ref ID J:41605] | ||
Genotyping Protocols
Gata1tm2sho, STD PCR, vers. 0
Helpful Links
Optimizing PCR Protocols
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]
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]
Gata1tm2Sho relatedCenturione 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]
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]
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; 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]
Colony Maintenance
Diet Information LabDiet® 5K52/5K67
| Pricing for USA, Canada and Mexico shipping destinations |
|
*Price(s) in US dollars ($)
Weeks of Age Price* Gender Cryorecovery Fee $1900.00
| Pricing for International shipping destinations |
|
*Price(s) in US dollars ($)
Weeks of Age Price* Gender Cryorecovery Fee $2470.00
| Standard Supply | Repository-Cryopreserved. Must Be Recovered. Please refer to pricing and supply notes for further information. |
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| Supply Notes |
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| Control | ||
|---|---|---|
| Wild-type from the colony | ||
| 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. | ||
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