Description

Strain Information

Type Mutant Stock; Targeted Mutation; Additional information on Genetically Engineered Mutant Mice. Species laboratory mouse Generation N?+2   Donating Investigator Richard Hynes,   Massachusetts Institute of Technology

Description
Mice that are heterozygous for the mutant allele are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. However, homozygous mice have an embryonic lethal phenotype, and die by embryonic day 10. The somites of the mutant embryos are small, irregularly shaped, and less cohesive compared with those of their wild-type littermates, and the epithelial organization of the somites is partially disrupted. Undulation of the neural tube is also observed in the mutant embryos. The mesodermal and endodermal cell layers of the yolk sac are separated in the mutants. The most dramatic cell adhesion defect is observed in the primitive heart; although myocardial tissue forms initially, the myocytes subsequently dissociate and the heart tube fails to develop normally.

Development
A BamHI-BamHI 8.3 kb fragment was isolated from lambda clone, MNG16. The BamHI genomic DNA fragment was subcloned into a plasmid containing the PMC1-HSVTK cassette. The neo expression cassette, PGKneobpA, was digested with XhoI/SalI, and subcloned into a unique SalI site in exon 10. The construct was linearized with NotI and electroporated into 129S2/SvPas-derived D3 ES cells, and colonies were selected with G418 and gancyclovir. A 2.4 kb SmaI-HindIII genomic DNA fragment located immediately 3' to the short arm of the targeting vector was used as a probe. The targeted ES clones were injected into blastocysts from C57BL/6J mice.

Related Strains

Strains carrying other alleles of Cdh2

007611

B6.129S6(SJL)-Cdh2tm1Glr/J

View Strains carrying other alleles of Cdh2     (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.

Cdh2^tm1Hyn/Cdh2^tm1Hyn

        involves: 129P2/OlaHsd

• lethality-prenatal/perinatal
• embryonic lethality during organogenesis (MGI Ref ID J:37888)
  • mutant embryos die by E10
• cardiovascular system phenotype
• abnormal cardiac muscle morphology (MGI Ref ID J:37888)
  • cardiac myoocytes surround the endocardium and are unable to develop a normal myocardium
• abnormal myocardial fiber morphology (MGI Ref ID J:37888)
  • cardiac myocytes tend to disaggregate
• abnormal heart tube morphology (MGI Ref ID J:37888)
  • all embryos examined between E9 and E10 exhibit a malformed heart tube
  • myocytes dissociated from heart tubes form loose aggregates that contract weakly in vitro compared to strong beating aggregates in wild-type
• distended pericardial sacs (MGI Ref ID J:37888)
  • expanded pericardial cavity occupies much of the amniotic cavity
• enlarged heart (MGI Ref ID J:37888)
  • seen as early as E8.5
• embryogenesis phenotype
• abnormal embryo turning (MGI Ref ID J:37888)
  • rarely turn completely from the lordotic to the fetal position
• abnormal somite shape (MGI Ref ID J:37888)
  • somites are small, irregularly shaped, and less cohesive at E8.5
• abnormal yolk sac morphology (MGI Ref ID J:37888)
  • exhibit separation of the mesodermal and endodermal cell layers of the yolk sac, however points of contact are still maintained between the two cell layers
• abnormal vitelline vasculature (MGI Ref ID J:37888)
  • blood vessels in the yolk sac are not appropriately formed
• embryonic growth retardation (MGI Ref ID J:37888)
  • significantly delayed by E9.5 and are equivalent in size to normal E9 embryos
• nervous system phenotype
• wavy neural tube (MGI Ref ID J:37888)
  • undulation of the neural tube
• muscle phenotype
• abnormal cardiac muscle morphology (MGI Ref ID J:37888)
  • cardiac myoocytes surround the endocardium and are unable to develop a normal myocardium
• abnormal myocardial fiber morphology (MGI Ref ID J:37888)
  • cardiac myocytes tend to disaggregate
• growth/size phenotype
• embryonic growth retardation (MGI Ref ID J:37888)
  • significantly delayed by E9.5 and are equivalent in size to normal E9 embryos

View Research Applications

Research Applications

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

Cdh2^tm1Hyn related

Cardiovascular Research
Heart Abnormalities

Cell Biology Research
Defects in Cell Adhesion Molecules

Developmental Biology Research
Defects in Cell Adhesion Molecules
Embryonic Lethality (Homozygous)
Internal/Organ Defects (heart)

Internal/Organ Research
Heart Abnormalities

Genes & Alleles

Gene & Allele Information

Allele Symbol		Cdh2tm1Hyn
Allele Name		targeted mutation 1, Richard O Hynes
Allele Type		Targeted (knock-out)
Common Name(s)		Cdh2-;
Mutation Made By		Richard Hynes,   Massachusetts Institute of Technology
Strain of Origin		129S2/SvPas
ES Cell Line Name		D3
ES Cell Line Strain		129S2/SvPas
Gene Symbol and Name		Cdh2, cadherin 2
Chromosome		18
Gene Common Name(s)		CD325; CDHN; CDw325; N-cadherin; NCAD; Ncad; cadherin, N-;
Molecular Note		A neomycin cassette was inserted into the exon 10, which encodes part of the extracellular domain of the protein. The protein was untectectable in Western blots of protein lysates derived from homozygous mutant embryos. [MGI Ref ID J:37888]

Genotyping

Genotyping Information

This strain will not have a genotyping protocol or one is not currently available.

Helpful Links

Optimizing PCR Protocols

References

References

Selected Reference(s)

Radice GL; Rayburn H; Matsunami H; Knudsen KA; Takeichi M; Hynes RO. 1997. Developmental defects in mouse embryos lacking N-cadherin. Dev Biol 181(1):64-78. [PubMed: 9015265]  [MGI Ref ID J:37888]

Additional References

Cdh2^tm1Hyn related

Edsbagge J; Johansson JK; Esni F; Luo Y; Radice GL; Semb H. 2005. Vascular function and sphingosine-1-phosphate regulate development of the dorsal pancreatic mesenchyme. Development 132(5):1085-92. [PubMed: 15689381]  [MGI Ref ID J:97177]

Esni F; Johansson BR; Radice GL; Semb H. 2001. Dorsal pancreas agenesis in N-cadherin- deficient mice. Dev Biol 238(1):202-12. [PubMed: 11784004]  [MGI Ref ID J:72022]

Horikawa K; Radice G; Takeichi M; Chisaka O. 1999. Adhesive subdivisions intrinsic to the epithelial somites. Dev Biol 215(2):182-9. [PubMed: 10545229]  [MGI Ref ID J:58409]

Kostetskii I; Li J; Xiong Y; Zhou R; Ferrari VA; Patel VV; Molkentin JD; Radice GL. 2005. Induced deletion of the N-cadherin gene in the heart leads to dissolution of the intercalated disc structure. Circ Res 96(3):346-54. [PubMed: 15662031]  [MGI Ref ID J:98828]

Lai CF; Cheng SL; Mbalaviele G; Donsante C; Watkins M; Radice GL; Civitelli R. 2006. Accentuated ovariectomy-induced bone loss and altered osteogenesis in heterozygous N-cadherin null mice. J Bone Miner Res 21(12):1897-906. [PubMed: 17002573]  [MGI Ref ID J:128076]

Luo Y; Ferreira-Cornwell M; Baldwin H; Kostetskii I; Lenox J; Lieberman M; Radice G. 2001. Rescuing the N-cadherin knockout by cardiac-specific expression of N- or E-cadherin. Development 128(4):459-69. [PubMed: 11171330]  [MGI Ref ID J:67158]

Luo Y; High FA; Epstein JA; Radice GL. 2006. N-cadherin is required for neural crest remodeling of the cardiac outflow tract. Dev Biol 299(2):517-28. [PubMed: 17014840]  [MGI Ref ID J:115264]

Luo Y; Radice GL. 2003. Cadherin-mediated adhesion is essential for myofibril continuity across the plasma membrane but not for assembly of the contractile apparatus. J Cell Sci 116(Pt 8):1471-9. [PubMed: 12640032]  [MGI Ref ID J:118482]

Health & husbandry

Health & Colony Maintenance Information

Colony Maintenance

Breeding & Husbandry	The strain exists on a mixed B6,129,CD1 background and can be maintained by heterozygous matings.

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.

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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Terms of Use

Terms of Use

General Terms and Conditions

For Licensing and Use Restrictions view the link(s) below:
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Contact information

General inquiries

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

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