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Former Names B6.129S7-Ephb4tm1And/J (Changed: 03-NOV-06 ) Type Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Species laboratory mouse Generation N2+1pN1
Generation DefinitionsDonating Investigator David Anderson, California Institute of Technology Description
Mice homozygous for this targeted mutation show growth retardation and lack of blood flow by embryonic day 9.5-10 (E9.5-10), with lethality occurring around this time. Expression of lacZ occurs exclusively in embryonic vascular endothelial cells and is preferentially expressed on veins. Homozygous embryos show defective angiogenic remodeling at the capillary plexus stage in both yolk sac and head. Arrested cardiac morphogenesis and defective myocardial trabecular extensions are also observed. Heterozygous mice are viable, fertile, exhibit no behavioral defects, and have identical lacZ expression patterns. These mutant mice may be useful in studying the cellular and molecular mechanisms underlying vasculogenesis and angiogenesis, the topography of neovascularization, and adult neovascularization, including tumor angiogenesis.The developmental abnormalities in homozygous mice closely resemble those observed for mutant mice bearing a lacZ-expressing null mutation of the Eph receptor B4 ligand (see Stock No. 006039 Efnb2tm1And).
Development
A targeting vector containing 5 Myc epitope tags fused to a tau-lacZ coding sequence immediately followed by a loxP-flanked PGK neo gene was used to replace the latter portion of exon 1 of the endogenous gene. This construct was inserted in-frame after the translational start ATG by microinjection into 129S7/SvEvBrd-derived AB1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts. The resulting chimeric males were bred to C57BL/6 females. Heterozygous mice were bred to C57BL/6 for approximately 2 generations.
| Control | ||
|---|---|---|
| Wild-type from the colony | ||
| 000664 C57BL/6J | ||
| Considerations for Choosing Controls | ||
lacZ Expression Strains
View lacZ Expression Strains (245 strains)
Strains carrying other alleles of lacZ
View Strains carrying other alleles of lacZ (217 strains)
Fluorescent Proteins/lacZ Systems
View Mammalian Phenotype Terms
Mammalian Phenotype Terms provided by MGI
assigned by genotype
Ephb4tm1And/Ephb4tm1And
involves: 129S7/SvEvBrd * C57BL/6J
- mortality/aging
- complete embryonic lethality during organogenesis
- embryogenesis phenotype
- abnormal vitelline vascular remodeling
- embryonic growth retardation
- apparent at E9.5-E10 (MGI Ref ID J:57908)
- cardiovascular system phenotype
- abnormal angiogenesis
- problems remodeling blood vessels apparently independent of heart defects (MGI Ref ID J:57908)
- abnormal heart morphology (MGI Ref ID J:57908)
- abnormal endocardium morphology
- endocardium fails to expand (MGI Ref ID J:57908)
- absent myocardial trabeculae
- failure of myocardial trabeculation by E10 (MGI Ref ID J:57908)
- failure of heart looping
- incomplete heart looping at E7.5-9 but heartbeat and blood flow still detectable (MGI Ref ID J:57908)
- small heart
- heart fails to enlarge between E9 and E9.5 (MGI Ref ID J:57908)
- abnormal vitelline vascular remodeling
- growth/size phenotype
- embryonic growth retardation
- apparent at E9.5-E10 (MGI Ref ID J:57908)
- muscle phenotype
- absent myocardial trabeculae
- failure of myocardial trabeculation by E10 (MGI Ref ID J:57908)
View Research Applications
Research Applications
This mouse can be used to support research in many areas including:
Cardiovascular Research
Vascular Defects
Developmental Biology Research
Embryonic Lethality (Homozygous)
Internal/Organ Defects
heart
heart: vasculature
vasculature
Research Tools
lacZ Expression
Cancer Research
endothelial cell marker for neovascularization
Cardiovascular Research
endothelial cell marker (lacZ) for neovascularization
endothelial cell marker for neovascularization
Developmental Biology Research
Genetics Research
Tissue/Cell Markers
Tissue/Cell Markers: endothelial cell markers for neovascularization
Tissue/Cell Markers: endothelial cells
| Allele Symbol | Ephb4tm1And | ||
|---|---|---|---|
| Allele Name | targeted mutation 1, David J Anderson | ||
| Allele Type | Targeted (Reporter) | ||
| Common Name(s) | EphB4taulacZ; | ||
| Mutation Made By | David Anderson, California Institute of Technology | ||
| Strain of Origin | 129S7/SvEvBrd-Hprt<+> | ||
| ES Cell Line Name | AB1 | ||
| ES Cell Line Strain | 129S7/SvEvBrd-Hprt<+> | ||
| Site of Expression | lacZ expression is detected in embryonic vascular endothelial cells and is preferentially expressed on veins. | ||
| Expressed Gene | lacZ, beta-galactosidase, E. coli | ||
| Molecular Note | A tau-lacZ-PGK-neo cassette replaced exon 1 and was fused in frame to the translation start codon via homologous recombination. Homozygous mutant embryos were identified by PCR genotyping at E9.5. [MGI Ref ID J:57908] | ||
| Gene Symbol and Name | Ephb4, Eph receptor B4 | ||
| Chromosome | 5 | ||
| Gene Common Name(s) | AI042935; HTK; Htk; MDK2; MYK1; TYRO11; expressed sequence AI042935; hepatoma transmembrane kinase; | ||
Genotyping Protocols
Ephb4tm1And, Standard PCR
Helpful Links
Genotyping resources and troubleshooting
Gerety SS; Wang HU; Chen ZF; Anderson DJ. 1999. Symmetrical mutant phenotypes of the receptor EphB4 and its specific transmembrane ligand ephrin-B2 in cardiovascular development. Mol Cell 4(3):403-14. [PubMed: 10518221] [MGI Ref ID J:57908]
Ephb4tm1And relatedCorada M; Nyqvist D; Orsenigo F; Caprini A; Giampietro C; Taketo MM; Iruela-Arispe ML; Adams RH; Dejana E. 2010. The Wnt/beta-catenin pathway modulates vascular remodeling and specification by upregulating Dll4/Notch signaling. Dev Cell 18(6):938-49. [PubMed: 20627076] [MGI Ref ID J:163848]
Dopeso H; Mateo-Lozano S; Mazzolini R; Rodrigues P; Lagares-Tena L; Ceron J; Romero J; Esteves M; Landolfi S; Hernandez-Losa J; Castano J; Wilson AJ; Ramon y Cajal S; Mariadason JM; Schwartz S Jr; Arango D. 2009. The receptor tyrosine kinase EPHB4 has tumor suppressor activities in intestinal tumorigenesis. Cancer Res 69(18):7430-8. [PubMed: 19738063] [MGI Ref ID J:152683]
Egawa G; Osawa M; Uemura A; Miyachi Y; Nishikawa S. 2009. Transient expression of ephrin b2 in perinatal skin is required for maintenance of keratinocyte homeostasis. J Invest Dermatol 129(10):2386-95. [PubMed: 19571816] [MGI Ref ID J:157054]
Kim YH; Hu H; Guevara-Gallardo S; Lam MT; Fong SY; Wang RA. 2008. Artery and vein size is balanced by Notch and ephrin B2/EphB4 during angiogenesis. Development 135(22):3755-64. [PubMed: 18952909] [MGI Ref ID J:144857]
Krebs LT; Starling C; Chervonsky AV; Gridley T. 2010. Notch1 activation in mice causes arteriovenous malformations phenocopied by ephrinB2 and EphB4 mutants. Genesis 48(3):146-50. [PubMed: 20101599] [MGI Ref ID J:163061]
Lavine KJ; Kovacs A; Ornitz DM. 2008. Hedgehog signaling is critical for maintenance of the adult coronary vasculature in mice. J Clin Invest 118(7):2404-14. [PubMed: 18568073] [MGI Ref ID J:137685]
Lavine KJ; Long F; Choi K; Smith C; Ornitz DM. 2008. Hedgehog signaling to distinct cell types differentially regulates coronary artery and vein development. Development 135(18):3161-71. [PubMed: 18725519] [MGI Ref ID J:138814]
Muto A; Yi T; Harrison KD; Davalos A; Fancher TT; Ziegler KR; Feigel A; Kondo Y; Nishibe T; Sessa WC; Dardik A. 2011. Eph-B4 prevents venous adaptive remodeling in the adult arterial environment. J Exp Med 208(3):561-75. [PubMed: 21339325] [MGI Ref ID J:177018]
Visconti RP; Richardson CD; Sato TN. 2002. Orchestration of angiogenesis and arteriovenous contribution by angiopoietins and vascular endothelial growth factor (VEGF). Proc Natl Acad Sci U S A 99(12):8219-24. [PubMed: 12048246] [MGI Ref ID J:77107]
Animal Health Reports
Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, RG10/RG30.Colony Maintenance
Breeding & Husbandry When maintaining a live colony, these mice are bred as heterozygotes. Homozygous mice die in utero.
| Pricing for USA, Canada and Mexico shipping destinations |
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Cryopreserved Mice - Ready for Recovery
Animals Provided
Price (US dollars $) Cryorecovery* $1980.00 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 for further information.
Supply Notes
- Cryorecovery - Standard.
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. The total number of animals provided, their gender and genotype will vary. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 13 and 16 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* $2574.00 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 for further information.
Supply Notes
- Cryorecovery - Standard.
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. The total number of animals provided, their gender and genotype will vary. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 13 and 16 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 for further information.
| Control | ||
|---|---|---|
| Wild-type from the colony | ||
| 000664 C57BL/6J | ||
| 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 requires a license prior to shipping.
| phone: | 207-288-6470 |
| fax: | 207-288-6655 |
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