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 Congenic; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Additional information on Congenic nomenclature. Species laboratory mouse Background Strain C57BL/6 Donor Strain 129S2 via D3 ES cell line Generation F6pF1   Donating Investigator Richard Hynes,   Massachusetts Institute of Technology

Description
Mice homozygous for the Cdh3^tm1Hyn targeted mutation (P-cadherin deficient) are viable and fertile with females able to nurse and maintain their litters. Virgin homozygous mutant females display precocious differentiation of the mammary gland. Aging mice develop hyperplasia and dysplasia of the mammary epithelium. In addition, mammary glands from P-cadherin deficient mice show abnormal lymphocyte infiltration.

Development
An EcoRI-EcoRI DNA 8.5 kb DNA fragment was isolated from lamda clone, PG21, and subcloned into Bluescript KS. The neo expression cassette, pMC1neo, was digested with XhoI-SalI and subcloned into a unique XhoI site in exon 11. The BamHI-BamHI DNA fragment was subcloned into a plasmid containing the pMC1-HSVTK cassette. The construct was linearized with NotI and electroporated into D3 ES cells, and colonies were selected with G418 and gancyclovir. An EcoRI-BamHI genomic 0.7 kb DNA fragment located immediately 5' to the short arm of the targeting vector was used as a probe. The targeted ES clones were injected into blastocysts from C57BL/6 mice.

Control Information

	Control
	000664 C57BL/6J
Considerations for Choosing Controls

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.

Cdh3^tm1Hyn/Cdh3^tm1Hyn

        involves: 129S2/SvPas * C57BL/6

• endocrine/exocrine gland phenotype
• abnormal mammary gland morphology (MGI Ref ID J:44359)
  • at 19-24 months of age, virgin female homozygotes exhibit extensive periductal lymphocyte infiltration into the interstitial space of mammary glands
• abnormal mammary gland development (MGI Ref ID J:44359)
  • at 10 weeks of age, mammary glands from postpubescent virgin female homoygotes show precocious alveolar differentiation and express casein(s) resembling early (day 14) pregnant wild-type glands
  • however, female homozygotes are fertile and able to nurse and maintain a normal size litter, and display normal branching of the mammary ductal tree up to 5 weeks of age
• mammary gland alveolar hyperplasia (MGI Ref ID J:44359)
  • at 19-24 months of age, virgin female homozygotes display focal mammary alveolar hyperplasia
  • secretory vacuoles are observed in alveoli of aging virgin homozygotes consistent with a differentiated hyperplastic phenotype
• mammary gland duct hyperplasia (MGI Ref ID J:44359)
  • at 19-24 months of age, virgin female homozygotes display mammary ductal dysplasia and stromal/fibroblastic hyperplasia with marked lymphocyte infiltration noted around the ducts
  • in contrast to the mammary duct epithelium which becomes hyperplastic, the surrounding monolayer of myoepithelial cells remains normal
• mammary gland hyperplasia (MGI Ref ID J:44359)
  • at 15 months of age, several multiparous females homozygotes display extensive mammary hyperplasia and dysplasia
  • however, no palpable mammary tumors are observed up to 2 years of age
• reproductive system phenotype
• abnormal mammary gland morphology (MGI Ref ID J:44359)
  • at 19-24 months of age, virgin female homozygotes exhibit extensive periductal lymphocyte infiltration into the interstitial space of mammary glands
• abnormal mammary gland development (MGI Ref ID J:44359)
  • at 10 weeks of age, mammary glands from postpubescent virgin female homoygotes show precocious alveolar differentiation and express casein(s) resembling early (day 14) pregnant wild-type glands
  • however, female homozygotes are fertile and able to nurse and maintain a normal size litter, and display normal branching of the mammary ductal tree up to 5 weeks of age
• mammary gland alveolar hyperplasia (MGI Ref ID J:44359)
  • at 19-24 months of age, virgin female homozygotes display focal mammary alveolar hyperplasia
  • secretory vacuoles are observed in alveoli of aging virgin homozygotes consistent with a differentiated hyperplastic phenotype
• mammary gland duct hyperplasia (MGI Ref ID J:44359)
  • at 19-24 months of age, virgin female homozygotes display mammary ductal dysplasia and stromal/fibroblastic hyperplasia with marked lymphocyte infiltration noted around the ducts
  • in contrast to the mammary duct epithelium which becomes hyperplastic, the surrounding monolayer of myoepithelial cells remains normal
• mammary gland hyperplasia (MGI Ref ID J:44359)
  • at 15 months of age, several multiparous females homozygotes display extensive mammary hyperplasia and dysplasia
  • however, no palpable mammary tumors are observed up to 2 years of age

View Research Applications

Research Applications

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

Cdh3^tm1Hyn related

Cancer Research
Defects in Cell Adhesion Molecules
Increased Tumor Incidence
      Mammary Gland Tumors

Genes & Alleles

Gene & Allele Information

Allele Symbol		Cdh3tm1Hyn
Allele Name		targeted mutation 1, Richard O Hynes
Allele Type		Targeted (knock-out)
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		Cdh3, cadherin 3
Chromosome		8
Gene Common Name(s)		AI385538; CDHP; Cadp; HJMD; P-cadherin; PCAD; Pcad; expressed sequence AI385538; placental cadherin;
Molecular Note		A neomycin phosphotransferase expression cassette was inserted into a unique XhoI site in exon 11. Western analysis of placental lysates from intercross progeny did not detect expression of the protein in homozygous mice. [MGI Ref ID J:44539]

Genotyping

Genotyping Information

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

Helpful Links

Genotyping resources and troubleshooting

References

References

Selected Reference(s)

Radice GL; Ferreira-Cornwell MC; Robinson SD; Rayburn H; Chodosh LA; Takeichi M; Hynes RO. 1997. Precocious mammary gland development in P-cadherin-deficient mice. J Cell Biol 139(4):1025-32. [PubMed: 9362520]  [MGI Ref ID J:44359]

Additional References

Cdh3^tm1Hyn related

Lenormand T; Fel-Clair F; Manolakou K; Alibert P; Britton-Davidian J. 1997. Chromosomal transmission bias in laboratory hybrids between wild strains of the two European subspecies of house mice. Genetics 147(3):1279-87. [PubMed: 9383070]  [MGI Ref ID J:44539]

Lenox JM; Koch PJ; Mahoney MG; Lieberman M; Stanley JR; Radice GL. 2000. Postnatal lethality of P-cadherin/desmoglein 3 double knockout mice: demonstration of a cooperative effect of these cell adhesion molecules in tissue homeostasis of stratified squamous epithelia. J Invest Dermatol 114(5):948-52. [PubMed: 10771476]  [MGI Ref ID J:62092]

Rhee H; Polak L; Fuchs E. 2006. Lhx2 maintains stem cell character in hair follicles. Science 312(5782):1946-9. [PubMed: 16809539]  [MGI Ref ID J:110119]

Tinkle CL; Pasolli HA; Stokes N; Fuchs E. 2008. New insights into cadherin function in epidermal sheet formation and maintenance of tissue integrity. Proc Natl Acad Sci U S A 105(40):15405-10. [PubMed: 18809908]  [MGI Ref ID J:144091]

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

Colony Maintenance

Breeding & Husbandry	This stain is on a C57BL/6 background and the current backcross generation is N5. The strain is maintained by homozygous matings. Homozygotes are viable and fertile.The donating lab maintained these mice by avoiding brother-sister matings. Expected coat color from breeding:Black
Diet Information	LabDiet® 5K52/5K67

Purchasing information

Pricing, Supply Level & Notes, Controls, General Terms & Conditions

Pricing

Supply Details

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). This strain is included in the Induced Mutant Resource Colony collection. Genomic DNA is available for this strain from the Mouse DNA Resource.

Control Information

	Control
	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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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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