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- Description
- Phenotype
- Genes & alleles
- Genotyping
- Health & husbandry
- References
- Purchasing information
- Terms of Use
Description
Strain Information
Type Congenic; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered Mutant Mice. Species laboratory mouse Generation N3+2F1PN1 Donating Investigator David Anderson, California Institute of Technology Description
Mice homozygous for this targeted mutation show growth retardation and enlargement of the heart at embryonic day 10 (E10), with 100% lethality occurring around E11. Reporter protein expression patterns are consistent with arterial, but not venous, expression of the endogenous gene; prominent lacZ signal is observed in hindbrain and somites, with lower levels in aorta and heart as early as E8.25. Expression in the yolk sac was first detected at E8.5, and is also observed in nephrogenic mesoderm and branchial arches. Homozygous embryos show defective angiogenic remodeling at the capillary plexus stage in both yolk sac and head. Endothelial vessel support cell differentiation of the yolk sac is also defective. Homozygotes lack myocardial trabecular extensions, and capillary ingrowth into the neural tube does not occur. 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 ephrin B2 receptor (see Stock No. 006044 Ephb4tm1And).
Development
A targeting vector was designed with a tau-lacZ coding sequence immediately followed by a PGKneo gene. This sequence was inserted in-frame after the translational start ATG and replaced the latter portion of exon 1 of the endogenous gene. The construct was microinjected into 129S7/SvEvBrd-derived AB1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts and the resulting chimeric males were bred to C57BL/6 females. Heterozygous mice were bred to C57BL/6 for at least 3 generations before arriving at The Jackson Laboratory. Upon arrival, heterozygotes were bred with C57BL/6J for more than two generations.
Control Information
| Control | ||
|---|---|---|
| Wild-type from the colony | ||
| 000664 C57BL/6J | ||
| Considerations for Choosing Controls | ||
Related Strains
lacZ Expression Strains
View lacZ Expression Strains (176 strains)
006042 B6.129S7-Efnb2tm2And/J 007843 B6;129S4-Efnb2tm2Sor/J
Additional Web Information
Congenic Nomenclature
Fluorescent Proteins/lacZ Systems
Phenotype
Phenotype Information
assigned by genotype
The following phenotype information may relate to a genetic background differing from this JAX® Mice strain.
Efnb2tm1And/Efnb2tm1And
involves: 129S7/SvEvBrd
- lethality-prenatal/perinatal
- embryonic lethality during organogenesis (MGI Ref ID J:75288)
- all homozygotes die by E11
- embryogenesis phenotype
- abnormal vitelline vasculature (MGI Ref ID J:75288)
- at E9.5, intercalation bidirectional growth of arteries and veins in the yolk sac is absent in mutants across the anterior-posterior compared to heterozygous controls
- defects in yolk sac angiogenesis are apparent at 9.0, becoming prominent at E9.5
- in the anterior region of the yolk sac, there is a block to remodeling at the capillary plexus stage for arterial and venous vessels at E9-9.5
- support cells in mutants are more rounded in appearance in contrast to the elongated support cells associated with the endothelial vessels in control heterozygotes at E10 and 10.5
- in contrast to heterozygote yolk sacs, capillary diameter appears relatively uniform between E9.5 through E10.5 rather than increasing; mutant capillaries fail to delaminate from the basal endodermal layer
- embryonic growth retardation (MGI Ref ID J:75288)
- apparent by E10
- growth/size phenotype
- embryonic growth retardation (MGI Ref ID J:75288)
- apparent by E10
- cardiovascular system phenotype
- *normal* cardiovascular system phenotype (MGI Ref ID J:75288)
- formation of major vessels in the trunk of the embryo is normal
- iintersomitic vessels originating from the dorsal aorta form normally at E9.5
- abnormal cardiac muscle morphology (MGI Ref ID J:119151)
- marker analysis indicates that ventricular myocardial differentiation is impaired
- failure of myocardial trabecular formation (MGI Ref ID J:75288)
- at E10, myocardial trabecular extensions are absent
- abnormal cardinal vein morphology (MGI Ref ID J:75288)
- anterior branches of the anterior cardinal vein form but are slightly dilated
- abnormal endocardium morphology (MGI Ref ID J:75288)
- between E8.5 and 9 primitive endocardium is only mildly perturbed compared to controls
- at E10, the endocardium shows pronounced disorganization
- abnormal heart ventricle morphology (MGI Ref ID J:119151)
- marker analysis indicates that ventricular myocardial differentiation is impaired
- however, ventricular cell proliferation is normal
- abnormal vasculogenesis (MGI Ref ID J:75288)
- embryonic angiogenesis is defective such that the capillary bed in the heads of mutant embryos appears dilated and apparently arrested at the primary plexus stage
- anterior-most branches of the internal carotid artery fail to develop
- capillary ingrowth into the neural tube fails to occur; endothelial cells remain associated with the surface of the developing spinal cord
- enlarged heart (MGI Ref ID J:75288)
- heart is enlarged in E10 embryos
- muscle phenotype
- abnormal cardiac muscle morphology (MGI Ref ID J:119151)
- marker analysis indicates that ventricular myocardial differentiation is impaired
- failure of myocardial trabecular formation (MGI Ref ID J:75288)
- at E10, myocardial trabecular extensions are absent
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)
Genes & Alleles
Gene & Allele Information
| Allele Symbol | Efnb2tm1And | ||
|---|---|---|---|
| Allele Name | targeted mutation 1, David J Anderson | ||
| Allele Type | Targeted (Reporter) | ||
| Common Name(s) | EphrinB2LacZ; EphrinB2tlacz; ephrin-B2tlacZ; | ||
| 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 hindbrain and somites, with lower levels detected in aorta and heart at embryonic day 8.25 (E8.25). Expression is detected in the yolk sac at E8.5 and is also detected in nephrogenic mesoderm and branchial arches. | ||
| Gene Symbol and Name | Efnb2, ephrin B2 | ||
| Chromosome | 8 | ||
| Gene Common Name(s) | ELF-2; EPLG5; Epl5; HTKL; Htk-L; LERK-5; LERK5; MGC126226; MGC126227; MGC126228; NLERK-1; eph-related receptor tyrosine kinase ligand 5; | ||
| Molecular Note | The targeting strategy involved deleting the signal sequence and fusing a tau-lacZ PGK-neomycin cassette in frame with the initiation codon. There was no expression of endogenous mRNA by in situ hybridization in homozygous mutant animals. Heterozygous embryos expressed beta-galactosidase in a pattern that was indistinguishable from the endogenous expression pattern. [MGI Ref ID J:75288] | ||
Genotyping
Genotyping Information
Genotyping Protocols
Efnb2tm1And, SEP PCR, vers. 1
Helpful Links
Optimizing PCR Protocols
References
References
Selected Reference(s)
Wang HU; Chen ZF; Anderson DJ. 1998. Molecular distinction and angiogenic interaction between embryonic arteries and veins revealed by ephrin-B2 and its receptor Eph-B4. Cell 93(5):741-53. [PubMed: 9630219] [MGI Ref ID J:75288]
Additional References
Efnb2tm1And relatedGerety SS; Anderson DJ. 2002. Cardiovascular ephrinB2 function is essential for embryonic angiogenesis. Development 129(6):1397-410. [PubMed: 11880349] [MGI Ref ID J:74909]
Grego-Bessa J; Luna-Zurita L; del Monte G; Bolos V; Melgar P; Arandilla A; Garratt AN; Zang H; Mukouyama YS; Chen H; Shou W; Ballestar E; Esteller M; Rojas A; Perez-Pomares JM; de la Pompa JL. 2007. Notch signaling is essential for ventricular chamber development. Dev Cell 12(3):415-29. [PubMed: 17336907] [MGI Ref ID J:119151]
Hayashi S; Asahara T; Masuda H; Isner JM; Losordo DW. 2005. Functional ephrin-B2 expression for promotive interaction between arterial and venous vessels in postnatal neovascularization. Circulation 111(17):2210-8. [PubMed: 15851594] [MGI Ref ID J:109693]
Krebs LT; Shutter JR; Tanigaki K; Honjo T; Stark KL; Gridley T. 2004. Haploinsufficient lethality and formation of arteriovenous malformations in Notch pathway mutants. Genes Dev 18(20):2469-73. [PubMed: 15466160] [MGI Ref ID J:93125]
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]
Mallory BP; Mead TJ; Wiginton DA; Kulkarni RM; Greenberg JM; Akeson AL. 2006. Lymphangiogenesis in the developing lung promoted by VEGF-A. Microvasc Res 72(1-2):62-73. [PubMed: 16806288] [MGI Ref ID J:129289]
Sorensen LK; Brooke BS; Li DY; Urness LD. 2003. Loss of distinct arterial and venous boundaries in mice lacking endoglin, a vascular-specific TGFbeta coreceptor. Dev Biol 261(1):235-50. [PubMed: 12941632] [MGI Ref ID J:85366]
Health & husbandry
Health & Colony Maintenance Information
Colony Maintenance
Breeding & Husbandry When maintaining a live colony, these mice are bred as heterozygotes. Homozygous mice die in utero.
Purchasing information
Pricing, Supply Level & Notes, Controls, General Terms & Conditions
Pricing
| Pricing for USA, Canada and Mexico shipping destinations |
|
*Price(s) in US dollars ($)
Weeks of Age Price* Gender Cryorecovery Fee $1900.00
Additional Supply Details
| Pricing for International shipping destinations |
|
*Price(s) in US dollars ($)
Weeks of Age Price* Gender Cryorecovery Fee $2470.00
Additional Supply Details
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Supply Details
| Standard Supply | Repository-Cryopreserved. Must Be Recovered. Please refer to pricing and supply notes for further information. |
|---|---|
| Supply Notes |
|
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
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Contact information
General inquiries
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| phone: | 207-288-6470 |
| fax: | 207-288-6655 |
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