Description

Strain Information

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 Information

	Control
	Wild-type from the colony
Considerations for Choosing Controls

Related Strains

Strains carrying other alleles of Gata1

005653

C.Cg-Gata1tm6Sho/J

View Strains carrying other alleles of Gata1     (1 strain)

Phenotype

Phenotype Information

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.

Gata1^tm2Sho/Gata1^tm2Sho

        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:

Gata1^tm2Sho related

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

Genes & Alleles

Gene & Allele Information

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

Genotyping Information

Genotyping Protocols

Gata1^tm2sho, STD PCR, vers. 0

Helpful Links

Optimizing PCR Protocols

References

References

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]

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]

Health & husbandry

Health & Colony Maintenance Information

Colony Maintenance

Diet Information	LabDiet® 5K52/5K67

Purchasing information

Pricing, Supply Level & Notes, Controls, General Terms & Conditions

Pricing

Supply Details

Standard Supply

Repository-Cryopreserved. Must Be Recovered. Please refer to pricing and supply notes for further information.

Supply Notes

Cryorecovery - Standard. The recovery process begins when a signed agreement form is returned to the Customer Service Department after order placement. Although results vary by strain, at least two males and two females (two pairs) will be provided, typically within 15 weeks of our receipt of the signed agreement form. If the first recovery attempt is unsuccessful or only one pair is recovered, a second recovery will be done, extending the delivery time to approximately 25 weeks. At least one member of each pair will be of known genotype and will carry the mutation if it is a mutant strain. Please note that pairs may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation of the strain. Mating schemes are sometimes modified for successful cryopreservation. Price represents a repository maintenance fee, which includes the cost of recovery of the strain from the cryopreservation resource and the periodic replacement of the frozen embryos used for recovery. Cryorecovery to establish a Dedicated Supply for greater quantities of mice. One to two pairs will be recovered to establish a Dedicated Supply of mice. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 or 1-207-288-5845. This strain is included in the Induced Mutant Resource Colony collection. Genomic DNA is available for this strain from the Mouse DNA Resource.

Control Information

	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.

General Terms and Conditions

See Terms of Use

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.

---

Ordering and Purchasing Information

      Purchasing Information
      JAX^® Mice Orders
      Surgical Services

Contact Information
Orders & Technical Support
Tel: 800.422.6423 or 207.288.5845
Fax: 207.288.6150
Technical Support Email Form

Terms of Use

Terms of Use

General Terms and Conditions

Effective September 26, 2007: License Requirements for Strains using Cre-lox Technology only apply in Canada, see Licenses for Strains using Cre-lox Technology.

For additional Licensing and Use Restrictions view the link(s) below:
- Use of MICE by companies or for-profit entities may require a license.

Contact information

General inquiries

Contracts Administration

phone:	207-288-6470
fax:	207-288-6655

JAX^® Mice & Services Conditions of Use

“Each recipient institution, including its employees and other researchers under its control (RECIPIENT), of mice or services using mice from The Jackson Laboratory (TJL) agrees that such mice, descendants of those mice derived by inbreeding or crossbreeding, including unmodified derivatives of those mice or their descendants (“MICE”) shall not be: (i) used for any purpose other than the internal research of the RECIPIENT, (ii) sold or otherwise provided to any third party for any use, or (iii) provided to any agent or other third party to provide breeding or other services with respect to MICE. Acceptance of MICE from TJL shall be deemed agreement by RECIPIENT to these conditions, and departure from these conditions requires The Jackson Laboratory’s prior written authorization.”

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, The Jackson Laboratory will, at its option, provide credit or replacement for the MICE or product received or the services provided.

No Liability

In no event shall The Jackson Laboratory, 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 The Jackson Laboratory, its agents or employees. In purchasing or receiving MICE, products or services from The Jackson Laboratory, purchaser or recipient, or any party claiming by or through them, expressly releases and discharges The Jackson Laboratory from all such causes of action or damages, and further agrees to defend and indemnify The Jackson Laboratory from any costs or damages arising out of any third party claims.

MICE and biological materials 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 The Jackson Laboratory’s MICE, products and services. In addition, special terms and conditions of sale of certain MICE, products and services may be set forth separately in The Jackson Laboratory 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 The Jackson Laboratory, 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 The Jackson Laboratory, 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 services by The Jackson Laboratory.