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 Mutant Stock; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Species laboratory mouse Generation N?+2 Generation Definitions   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 provided by MGI

      assigned by genotype

The following phenotype information may relate to a genetic background differing from this JAX^® Mice strain.

Cdh2^tm1Hyn/Cdh2^tm1Hyn

        involves: 129S2/SvPas

• mortality/aging
• complete embryonic lethality during organogenesis
  • mutant embryos die by E10   (MGI Ref ID J:37888)
• embryogenesis phenotype
• abnormal embryo turning
  • rarely turn completely from the lordotic to the fetal position   (MGI Ref ID J:37888)
• abnormal somite shape
  • at E8.5, somites are small, irregularly shaped, and less cohesive   (MGI Ref ID J:37888)
  • at E9.0, epithelial somites are smaller and irregular in size and shape   (MGI Ref ID J:58409)
  • epithelial somites are cleaved into rostral and caudal halves immediately after somite formation   (MGI Ref ID J:58409)
  • however, most of these fragmented somites maintain epithelial, vesicle-like structures   (MGI Ref ID J:58409)
• abnormal visceral yolk sac morphology
  • 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   (MGI Ref ID J:37888)
• abnormal vitelline vasculature morphology
  • blood vessels in the yolk sac are not appropriately formed   (MGI Ref ID J:37888)
• embryonic growth retardation
  • significantly delayed by E9.5 and are equivalent in size to normal E9 embryos   (MGI Ref ID J:37888)
• wavy neural tube
  • undulation of the neural tube   (MGI Ref ID J:37888)
• cardiovascular system phenotype
• abnormal heart tube morphology
  • all embryos examined between E9 and E10 exhibit a malformed heart tube   (MGI Ref ID J:37888)
  • myocytes dissociated from heart tubes form loose aggregates that contract weakly in vitro compared to strong beating aggregates in wild-type   (MGI Ref ID J:37888)
• abnormal myocardium layer morphology
  • cardiac myoocytes surround the endocardium and are unable to develop a normal myocardium   (MGI Ref ID J:37888)
• • abnormal myocardial fiber morphology
    • cardiac myocytes tend to disaggregate   (MGI Ref ID J:37888)
• abnormal vitelline vasculature morphology
  • blood vessels in the yolk sac are not appropriately formed   (MGI Ref ID J:37888)
• distended pericardium
  • expanded pericardial cavity occupies much of the amniotic cavity   (MGI Ref ID J:37888)
• enlarged heart
  • seen as early as E8.5   (MGI Ref ID J:37888)
• growth/size phenotype
• embryonic growth retardation
  • significantly delayed by E9.5 and are equivalent in size to normal E9 embryos   (MGI Ref ID J:37888)
• nervous system phenotype
• wavy neural tube
  • undulation of the neural tube   (MGI Ref ID J:37888)
• muscle phenotype
• abnormal myocardial fiber morphology
  • cardiac myocytes tend to disaggregate   (MGI Ref ID J:37888)

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 provided by MGI

Allele Symbol		Cdh2tm1Hyn
Allele Name		targeted mutation 1, Richard Hynes
Allele Type		Targeted (knock-out)
Common Name(s)		Cdh2-; N-cadherin-;
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

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

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]

Plageman TF Jr; Zacharias AL; Gage PJ; Lang RA. 2011. Shroom3 and a Pitx2-N-cadherin pathway function cooperatively to generate asymmetric cell shape changes during gut morphogenesis. Dev Biol 357(1):227-34. [PubMed: 21726547]  [MGI Ref ID J:175443]

Pontoriero GF; Smith AN; Miller LA; Radice GL; West-Mays JA; Lang RA. 2009. Co-operative roles for E-cadherin and N-cadherin during lens vesicle separation and lens epithelial cell survival. Dev Biol 326(2):403-17. [PubMed: 18996109]  [MGI Ref ID J:145191]

Smith AN; Miller LA; Radice G; Ashery-Padan R; Lang RA. 2009. Stage-dependent modes of Pax6-Sox2 epistasis regulate lens development and eye morphogenesis. Development 136(17):2977-85. [PubMed: 19666824]  [MGI Ref ID J:158133]

Health & husbandry

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.

Health & Colony Maintenance Information

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, RG10/RG30.

Colony Maintenance

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

Purchasing information

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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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