| |||||||||||||||||||
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 | ||
|---|---|---|
| Wild-type from the colony | ||
| Considerations for Choosing Controls | ||
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)
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.
Gata1tm2Sho/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
- cellular phenotype
- abnormal megakaryocyte differentiation (MGI Ref ID J:41605)
Gata1tm2Sho/Gata1tm2Sho
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)
Gata1tm2Sho/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)
- 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)
Gata1tm2Sho/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
- decreased bone marrow cell number
- bone marrow contains 3 times fewer cells than wild-type (MGI Ref ID J:78540)
- decreased platelet cell number
- enlarged spleen
- 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
- enlarged spleen
- 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:
Gata1tm2Sho relatedInternal/Organ Research
Skeleton
Bone
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 | 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 Protocols
Gata1tm2sho, Standard PCR
Helpful Links
Genotyping resources and troubleshooting
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]
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]
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 for USA, Canada and Mexico shipping destinations |
|
Cryopreserved Mice - Ready for Recovery
Animals Provided
Price (US dollars $) Cryorecovery* $2085.00 At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.
Standard Supply
Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.
Supply Notes
Cryorecovery - Standard.
Progeny testing is not required.
The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided, their gender and genotype will vary. We will fulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 11 and 14 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks. IMPORTANT NOTE: The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.Cryorecovery to establish a Dedicated Supply for greater quantities of mice
Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location).
| Pricing for International shipping destinations |
|
Cryopreserved Mice - Ready for Recovery
Animals Provided
Price (US dollars $) Cryorecovery* $2710.50 At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.
Standard Supply
Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.
Supply Notes
Cryorecovery - Standard.
Progeny testing is not required.
The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided, their gender and genotype will vary. We will fulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 11 and 14 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks. IMPORTANT NOTE: The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.Cryorecovery to establish a Dedicated Supply for greater quantities of mice
Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location).
|
|
Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.
| Control | ||
|---|---|---|
| Wild-type from the colony | ||
| Considerations for Choosing Controls | ||
| Control Pricing Information for Genetically Engineered Mutant Strains. | ||
For Licensing and Use Restrictions view the link(s) below:
- Use of MICE by companies or for-profit entities may require a license.
| phone: | 207-288-6470 |
| fax: | 207-288-6655 |
MICE, PRODUCTS AND SERVICES ARE PROVIDED “AS IS”. JACKSON EXTENDS NO WARRANTIES OF ANY KIND, EITHER EXPRESS, IMPLIED, OR STATUTORY, WITH RESPECT TO MICE, PRODUCTS OR SERVICES, INCLUDING ANY IMPLIED WARRANTY OF MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE, OR ANY WARRANTY OF NON-INFRINGEMENT OF ANY PATENT, TRADEMARK, OR OTHER INTELLECTUAL PROPERTY RIGHTS.
In case of dissatisfaction for a valid reason and claimed in writing by a purchaser within ninety (90) days of receipt of mice, products or services, JACKSON will, at its option, provide credit or replacement for the mice or product received or the services provided.
In no event shall JACKSON, its trustees, directors, officers, employees, and affiliates be liable for any causes of action or damages, including any direct, indirect, special, or consequential damages, arising out of the provision of MICE, PRODUCTS or services, including economic damage or injury to property and lost profits, and including any damage arising from acts or negligence on the part of JACKSON, its agents or employees. Unless prohibited by law, in purchasing or receiving MICE, PRODUCTS or services from JACKSON, purchaser or recipient, or any party claiming by or through them, expressly releases and discharges JACKSON from all such causes of action or damages, and further agrees to defend and indemnify JACKSON from any costs or damages arising out of any third party claims.
MICE and PRODUCTS are to be used in a safe manner and in accordance with all applicable governmental rules and regulations.
The foregoing represents the General Terms and Conditions applicable to JACKSON’s MICE, PRODUCTS or services. In addition, special terms and conditions of sale of certain MICE, PRODUCTS or services may be set forth separately in JACKSON web pages, catalogs, price lists, contracts, and/or other documents, and these special terms and conditions shall also govern the sale of these MICE, PRODUCTS and services by JACKSON, and by its licensees and distributors.
Acceptance of delivery of MICE, PRODUCTS or services shall be deemed agreement to these terms and conditions. No purchase order or other document transmitted by purchaser or recipient that may modify the terms and conditions hereof, shall be in any way binding on JACKSON, and instead the terms and conditions set forth herein, including any special terms and conditions set forth separately, shall govern the sale of MICE, PRODUCTS or services by JACKSON.