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Former Names B6.129S7-Ephb4tm1And/J (Changed: 03-NOV-06 ) Type Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered Mutant Mice. Mating System +/+ sibling x Hemizygote (Female x Male) Species laboratory mouse Generation N2+N3F3 (12-MAY-08) Donating 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 | ||
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| Wild-type from the colony | ||
| 000664 C57BL/6J | ||
| Considerations for Choosing Controls | ||
lacZ Expression Strains
View lacZ Expression Strains (176 strains)
Fluorescent Proteins/lacZ Systems
View Mammalian Phenotype Terms
Mammalian Phenotype Terms
assigned by genotype
Ephb4tm1And/Ephb4tm1And
involves: 129S7/SvEvBrd * C57BL/6J
- lethality-prenatal/perinatal
- embryonic lethality during organogenesis (MGI Ref ID J:57908)
- growth retardation, arrested heart development and lack of blood flow by E9.5-E10
- degeneration and necrosis by E10.5
- embryogenesis phenotype
- abnormal vitelline vascular remodeling (MGI Ref ID J:57908)
- remodeling defects most severe at the primitive plexus stage around E9.5
- most severe "on the venous side"
- embryonic growth retardation (MGI Ref ID J:57908)
- apparent at E9.5-E10
- cardiovascular system phenotype
- abnormal angiogenesis (MGI Ref ID J:57908)
- problems remodeling blood vessels apparently independent of heart defects
- abnormal vein development (MGI Ref ID J:57908)
- failure to remodel multiple small vessels into a single larger vessel
- failure of vascular branching (MGI Ref ID J:57908)
- fine branching of the head vasculature not seen at E9.5-10 but extensive fusion of the capillary network
- both arterial and venous intersomatic vessels fused and truncated
- abnormal anterior cardinal vein morphology (MGI Ref ID J:57908)
- development of the anterior cardinal vein is disrupted
- abnormal heart morphology (MGI Ref ID J:57908)
- abnormal endocardium morphology (MGI Ref ID J:57908)
- endocardium fails to expand
- failure of looping morphogenesis (MGI Ref ID J:57908)
- incomplete heart looping at E7.5-9 but heartbeat and blood flow still detectable
- failure of myocardial trabecular formation (MGI Ref ID J:57908)
- failure of myocardial trabeculation by E10
- small heart (MGI Ref ID J:57908)
- heart fails to enlarge between E9 and E9.5
- growth/size phenotype
- embryonic growth retardation (MGI Ref ID J:57908)
- apparent at E9.5-E10
- muscle phenotype
- failure of myocardial trabecular formation (MGI Ref ID J:57908)
- failure of myocardial trabeculation by E10
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: vasculature)
Internal/Organ Defects (vasculature)
Research Tools
lacZ Expression
Cancer Research (endothelial cell marker for neovascularization)
Cardiovascular Research (endothelial cell marker (lacZ) for neovascularization)
Cardiovascular Research (endothelial cell marker for neovascularization)
Developmental Biology Research
Genetics Research (Tissue/Cell Markers: endothelial cell markers for neovascularization)
Genetics Research (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-Hprt1<+> | ||
| ES Cell Line Name | AB1 | ||
| ES Cell Line Strain | 129S7/SvEvBrd-Hprt1<+> | ||
| Site of Expression | lacZ expression is detected in embryonic vascular endothelial cells and is preferentially expressed on veins. | ||
| 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; | ||
| 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] | ||
Genotyping Protocols
Ephb4tm1And, STD PCR, vers. 1
Helpful Links
Optimizing PCR Protocols
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 relatedLavine 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]
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
Room Number AX11
Colony Maintenance
Breeding & Husbandry When maintaining a live colony, these mice are bred as heterozygotes. Homozygous mice die in utero. Mating System +/+ sibling x Hemizygote (Female x Male) Diet Information LabDiet® 5K52/5K67
| Pricing for USA, Canada and Mexico shipping destinations |
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Weeks of Age Price* Gender Genotypes Provided Individual Mouse Price $236.40 Female or Male Heterozygous for Ephb4tm1And *Price(s) in US dollars ($)
Pairs /Price* Pair Genotype $288.65 Heterozygous for Ephb4tm1And x Wild-type for Ephb4tm1And $288.65 Wild-type for Ephb4tm1And x Heterozygous for Ephb4tm1And
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| Pricing for International shipping destinations |
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Weeks of Age Price* Gender Genotypes Provided Individual Mouse Price $307.40 Female or Male Heterozygous for Ephb4tm1And *Price(s) in US dollars ($)
Pairs /Price* Pair Genotype $375.30 Heterozygous for Ephb4tm1And x Wild-type for Ephb4tm1And $375.30 Wild-type for Ephb4tm1And x Heterozygous for Ephb4tm1And
| Supply Notes |
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| Standard Supply | Repository-Live. A collection of over 1000 strains maintained as live colonies. Individual colonies are sized to meet current customer demand. Delivery for orders of 10 mice or less ranges on average from one to eight weeks; mice are generally shipped between four to six weeks of age with a maximum shipping age of ~nine weeks. Colony sizes do not generally support stringent age specifications for large volumes of mice; however custom orders and larger quantities of mice are easily arranged. Estimated ship dates for all orders provided within 48 hours of order placement. |
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| Supply Notes |
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| 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. | ||
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