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 Congenic; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Additional information on Congenic nomenclature. Species laboratory mouse Background Strain C57BL/6J Donor Strain 129S4 via J1 ES cell line Generation N7   Donating Investigator IMR Colony,   The Jackson Laboratory

Description
90% of the homozygotes die within the first week of life. They display profound thrombocytopenia (no detectable circulating blood platelets) and megakaryocytes that show a maturation arrest characterized by failure to organize demarcatoin membranes and delimit platelet territories. Those that survive are anemic and display additional sporadic mortality of 10-20%. Male homozygotes are fertile.

Control Information

	Control
	Wild-type from the colony
	000664 C57BL/6J
Considerations for Choosing Controls

Additional Web Information

Congenic Nomenclature

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.

Nfe2^tm1Sho/Nfe2⁺

        C.129S4-Nfe2^tm1Sho

• life span-post-weaning/aging
• abnormal induced morbidity/mortality (MGI Ref ID J:125982)
  • mice exhibit a slightly quicker average time between exposure to the Friend virus and sacrifice compared to wild-type mice
• immune system phenotype
• enlarged spleen (MGI Ref ID J:125982)
  • following exposure with the Friend virus, mice exhibit an increase in spleen size compared to similarly treated wild-type mice
• increased susceptibility to viral infection (MGI Ref ID J:125982)
  • mice exhibit a slightly quicker average time between exposure to the Friend virus and sacrifice compared to wild-type mice
  • following exposure with the Friend virus, mice exhibit a shorter time span to tumor development and an increase in tumorigenic spleen volume compared to wild-type mice
• tumorigenesis
• increased incidence of induced tumors (MGI Ref ID J:125982)
  • following exposure with the Friend virus, mice exhibit a shorter time span to tumor development and an increase in tumorigenic spleen volume compared to wild-type mice
• hematopoietic system phenotype
• enlarged spleen (MGI Ref ID J:125982)
  • following exposure with the Friend virus, mice exhibit an increase in spleen size compared to similarly treated wild-type mice

Nfe2^tm1Sho/Nfe2^tm1Sho

        involves: 129/Sv * 129S4/SvJae

• lethality-prenatal/perinatal
• neonatal lethality (MGI Ref ID J:20132)
  • a majority of mice die during the neonatal period due to hemorrhage
• lethality-postnatal
• postnatal lethality (MGI Ref ID J:20132)
  • less than 10% of mice survive to adulthood
• life span-post-weaning/aging
• decreased survivor rate (MGI Ref ID J:20132)
  • less than 10% of mice survive to adulthood
• hematopoietic system phenotype
• abnormal hematopoietic system physiology (MGI Ref ID J:20132)
  • despite normal thrombopoeitin action, late megakaryocyte maturation is blocked
  • megakaryocytes are larger than normal and exhibit markers of maturity but never generate proplatelets even after prolonged culture conditions in which wild-type megakaryocytes produce proplatelets
• abnormal megakaryocyte morphology (MGI Ref ID J:20132)
  • megakaryocytes exhibit an increase in size compared to in wild-type mice, a paucity of granules, hyperlobation of the nucleus and emperipoiesis
  • megakaryocytes are larger than normal and exhibit markers of maturity but never generate proplatelets even after prolonged culture conditions in which wild-type megakaryocytes produce proplatelets
• decreased platelet cell number (MGI Ref ID J:106670)
  • mice exhibit thrombocytopenia that is cell autonomous
• absent platelets (MGI Ref ID J:20132)
• increased megakaryocyte cell number (MGI Ref ID J:20132)
  • 2- to 4-fold compared to in wild-type mice
• anemia (MGI Ref ID J:20132)
  • mice that survive into adulthood exhibit intermittent anemia
• decreased hemoglobin content (MGI Ref ID J:20132)
  • mice exhibit decreased hemoglobin content that cannot be explained by blood loss or iron deficiency
• 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
• microcytosis (MGI Ref ID J:20132)
  • mice exhibit microcytosis that cannot be explained by blood loss or iron deficiency
• 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 20-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
• cardiovascular system phenotype
• internal hemorrhage (MGI Ref ID J:20132)
  • after birth mice exhibit internal hemorrhages in the peritoneal cavity and the wall of the urinary bladder
  • a majority of mice die during the neonatal period due to hemorrhage
• skin/coat/nails phenotype
• pallor (MGI Ref ID J:20132)
  • after birth
• 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
• growth/size phenotype
• decreased body size (MGI Ref ID J:20132)

Nfe2^tm1Sho/Nfe2^tm1Sho

        involves: 129S4/SvJae * C57BL/6J

• lethality-prenatal/perinatal
• neonatal lethality (MGI Ref ID J:20132)
  • a majority of mice die during the neonatal period due to hemorrhage
• lethality-postnatal
• postnatal lethality (MGI Ref ID J:20132)
  • less than 10% of mice survive to adulthood
• life span-post-weaning/aging
• decreased survivor rate (MGI Ref ID J:20132)
  • less than 10% of mice survive to adulthood
• hematopoietic system phenotype
• abnormal hematopoietic system physiology (MGI Ref ID J:20132)
  • despite normal thrombopoeitin action, late megakaryocyte maturation is blocked
• abnormal megakaryocyte morphology (MGI Ref ID J:20132)
  • megakaryocytes exhibit an increase in size compared to in wild-type mice, a paucity of granules, hyperlobation of the nucleus and emperipoiesis
• absent platelets (MGI Ref ID J:20132)
• increased megakaryocyte cell number (MGI Ref ID J:20132)
  • 2- to 4-fold compared to in wild-type mice
• anemia (MGI Ref ID J:20132)
  • mice that survive into adulthood exhibit intermittent anemia
• decreased hemoglobin content (MGI Ref ID J:20132)
  • mice exhibit decreased hemoglobin content that cannot be explained by blood loss or iron deficiency
• microcytosis (MGI Ref ID J:20132)
  • mice exhibit microcytosis that cannot be explained by blood loss or iron deficiency
• cardiovascular system phenotype
• internal hemorrhage (MGI Ref ID J:20132)
  • after birth mice exhibit internal hemorrhages in the peritoneal cavity and the wall of the urinary bladder
  • a majority of mice die during the neonatal period due to hemorrhage
• skin/coat/nails phenotype
• pallor (MGI Ref ID J:20132)
  • after birth
• growth/size phenotype
• decreased body size (MGI Ref ID J:20132)

View Research Applications

Research Applications

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

Nfe2^tm1Sho related

Hematological Research
Anemia, Iron Deficiency and Transport Defects
Platelet Defects

Genes & Alleles

Gene & Allele Information

Allele Symbol		Nfe2tm1Sho
Allele Name		targeted mutation 1, Stuart Orkin
Allele Type		Targeted (knock-out)
Common Name(s)		NF-E2-; p45 NF-E2-; p45NFE2-;
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		Nfe2, nuclear factor, erythroid derived 2
Chromosome		15
Gene Common Name(s)		NF-E2; p45; p45NFE2; p45nf-e2;
Molecular Note		A PGK-neomycin cassette was inserted into exon 3, immediately upstream of sequences required for DNA binding and protein dimerization. Absence of intact mRNA and protein were demonstrated by Northern and immunoblot analyses, respectively. [MGI Ref ID J:20132]

Genotyping

Genotyping Information

Genotyping Protocols

Nfe2^tm1Sho, STD PCR, vers. 2

Helpful Links

Optimizing PCR Protocols

References

References

Selected Reference(s)

Shivdasani RA; Rosenblatt MF; Zucker-Franklin D; Jackson CW; Hunt P; Saris CJ; Orkin SH. 1995. Transcription factor NF-E2 is required for platelet formation independent of the actions of thrombopoietin/MGDF in megakaryocyte development. Cell 81(5):695-704. [PubMed: 7774011]  [MGI Ref ID J:20132]

Additional References

Nfe2^tm1Sho related

Camerer E; Qazi AA; Duong DN; Cornelissen I; Advincula R; Coughlin SR. 2004. Platelets, protease-activated receptors, and fibrinogen in hematogenous metastasis. Blood 104(2):397-401. [PubMed: 15031212]  [MGI Ref ID J:92278]

Chan JY; Kwong M; Lo M; Emerson R; Kuypers FA. 2001. Reduced oxidative-stress response in red blood cells from p45NFE2-deficient mice. Blood 97(7):2151-8. [PubMed: 11264184]  [MGI Ref ID J:68424]

Derjuga A; Gourley TS; Holm TM; Heng HH; Shivdasani RA; Ahmed R; Andrews NC; Blank V. 2004. Complexity of CNC transcription factors as revealed by gene targeting of the Nrf3 locus. Mol Cell Biol 24(8):3286-94. [PubMed: 15060151]  [MGI Ref ID J:89893]

Hamilton JR; Cornelissen I; Coughlin SR. 2004. Impaired hemostasis and protection against thrombosis in protease-activated receptor 4-deficient mice is due to lack of thrombin signaling in platelets. J Thromb Haemost 2(8):1429-35. [PubMed: 15304051]  [MGI Ref ID J:102309]

Kacena MA; Gundberg CM; Nelson T; Horowitz MC. 2005. Loss of the transcription factor p45 NF-E2 results in a developmental arrest of megakaryocyte differentiation and the onset of a high bone mass phenotype. Bone 36(2):215-23. [PubMed: 15780947]  [MGI Ref ID J:97981]

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]

Kerrigan SW; Gaur M; Murphy RP; Shattil SJ; Leavitt AD. 2004. Caspase-12: a developmental link between G-protein-coupled receptors and integrin alphaIIbbeta3 activation. Blood 104(5):1327-34. [PubMed: 15059849]  [MGI Ref ID J:92696]

Kuroha T; Takahashi S; Komeno T; Itoh K; Nagasawa T; Yamamoto M. 1998. Ablation of Nrf2 function does not increase the erythroid or megakaryocytic cell lineage dysfunction caused by p45 NF-E2 gene disruption. J Biochem (Tokyo) 123(3):376-9. [PubMed: 9538217]  [MGI Ref ID J:48007]

Lecine P; Italiano JE Jr; Kim SW; Villeval JL; Shivdasani RA. 2000. Hematopoietic-specific beta 1 tubulin participates in a pathway of platelet biogenesis dependent on the transcription factor NF-E2. Blood 96(4):1366-73. [PubMed: 10942379]  [MGI Ref ID J:63962]

Lecine P; Villeval JL; Vyas P; Swencki B; Xu Y; Shivdasani RA. 1998. Mice lacking transcription factor NF-E2 provide in vivo validation of the proplatelet model of thrombocytopoiesis and show a platelet production defect that is intrinsic to megakaryocytes. Blood 92(5):1608-16. [PubMed: 9716588]  [MGI Ref ID J:106670]

Levin J; Peng JP; Baker GR; Villeval JL; Lecine P; Burstein SA; Shivdasani RA. 1999. Pathophysiology of thrombocytopenia and anemia in mice lacking transcription factor NF-E2. Blood 94(9):3037-47. [PubMed: 10556187]  [MGI Ref ID J:79135]

Li YJ; Higgins RR; Pak BJ; Shivdasani RA; Ney PA; Archer M; Ben-David Y. 2001. p45(NFE2) is a negative regulator of erythroid proliferation which contributes to the progression of Friend virus-induced erythroleukemias. Mol Cell Biol 21(1):73-80. [PubMed: 11113182]  [MGI Ref ID J:125982]

Loyd MR; Okamoto Y; Randall MS; Ney PA. 2003. Role of AP1/NFE2 binding sites in endogenous alpha-globin gene transcription. Blood 102(12):4223-8. [PubMed: 12920035]  [MGI Ref ID J:86682]

Martin F; van Deursen JM; Shivdasani RA; Jackson CW; Troutman AG; Ney PA. 1998. Erythroid maturation and globin gene expression in mice with combined deficiency of NF-E2 and nrf-2. Blood 91(9):3459-66. [PubMed: 9558405]  [MGI Ref ID J:47440]

Palumbo JS; Zogg M; Talmage KE; Degen JL; Weiler H; Isermann BH. 2004. Role of fibrinogen- and platelet-mediated hemostasis in mouse embryogenesis and reproduction. J Thromb Haemost 2(8):1368-79. [PubMed: 15304043]  [MGI Ref ID J:102317]

Pappu R; Schwab SR; Cornelissen I; Pereira JP; Regard JB; Xu Y; Camerer E; Zheng YW; Huang Y; Cyster JG; Coughlin SR. 2007. Promotion of lymphocyte egress into blood and lymph by distinct sources of sphingosine-1-phosphate. Science 316(5822):295-8. [PubMed: 17363629]  [MGI Ref ID J:120783]

Schulze H; Korpal M; Bergmeier W; Italiano JE Jr; Wahl SM; Shivdasani RA. 2004. Interactions between the megakaryocyte/platelet-specific beta1 tubulin and the secretory leukocyte protease inhibitor SLPI suggest a role for regulated proteolysis in platelet functions. Blood 104(13):3949-57. [PubMed: 15315966]  [MGI Ref ID J:95293]

Shivdasani RA; Orkin SH. 1995. Erythropoiesis and globin gene expression in mice lacking the transcription factor NF-E2. Proc Natl Acad Sci U S A 92(19):8690-4. [PubMed: 7567998]  [MGI Ref ID J:77275]

Sood R; Sholl L; Isermann B; Zogg M; Coughlin SR; Weiler H. 2008. Maternal Par4 and platelets contribute to defective placenta formation in mouse embryos lacking thrombomodulin. Blood 112(3):585-91. [PubMed: 18490515]  [MGI Ref ID J:138440]

Tiwari S; Italiano JE Jr; Barral DC; Mules EH; Novak EK; Swank RT; Seabra MC; Shivdasani RA. 2003. A role for Rab27b in NF-E2-dependent pathways of platelet formation. Blood 102(12):3970-9. [PubMed: 12907454]  [MGI Ref ID J:86678]

Health & husbandry

Health & Colony Maintenance Information

Currently there no information available for this strain. This may be due to the supply level of this strain.

Purchasing information

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

Pricing

Supply Details

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes for further information.

Supply Notes

Cryorecovery - Standard. At least two mice that carry the mutation (if it is a mutant strain) will be provided. The total number of animals provided, their gender and genotype will vary. Please inquire if larger numbers of animals with specific genotypes and genders are needed. IMPORTANT NOTE: The genotypes of the 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 for possible genotypes for this specific strain. Animals typically ship within 13 to 16 weeks from your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will typically ship within 25 weeks. 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
	000664 C57BL/6J
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.

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Ordering and Purchasing Information

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Contact Information
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Tel: 800.422.6423 or 207.288.5845
Fax: 207.288.6150
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Terms of Use

Terms of Use

General Terms and Conditions

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.

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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.