Overview

Also Known As:Adam15 E>A

The Adam15 E>A knockin mice carry a point mutation that inactivates the catalytically active zinc-dependent metalloprotease domain resulting reduced tumor development in a heterotopic tumor injection model.

Donating Investigator

Carl P Blobel, Hospital for Special Surgery-Weill Med

Genetic overview

Genetic Background	Generation

Adam15^tm2.1Bbl

Allele Type	Gene Symbol	Gene Name
Targeted (Not Applicable)	Adam15	a disintegrin and metallopeptidase domain 15 (metargidin)

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Research Applications

Cancer Research

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Details

Detailed Description

Adam15 or a disintegrin and metallopeptidase domain 15 (metargidin) encodes a membrane-anchored metalloproteinase. Members of the ADAM family are involved in pathological neovascularization and are associated with cancer, atherosclerosis, RA and osteoarthritis. The Adam15 E>A knockin allele inactivates the catalytically active zinc-dependent metalloprotease domain. Mice homozygous for the mutation are viable and fertile. When injected heterotopically with melanoma cells, Adam15 E>A mice form fewer and smaller tumors than wild-type mice. This strain may be useful for studying the catalytic domain in Adam15 and tumor development.

Development

The targeting vector was designed to insert an E>A point mutation into exon 11 by site-directed mutagenesis. An FRT-flanked neomycin cassette was inserted downstream of exon 11. The mutation results in an A to C change at nucleotide 6829 altering the corresponding amino acid from glutamate to alanine.

The construct was electroporated into unspecified embryonic stem (ES) cells derived from 129P2/OlaHsd mice. Correctly targeted ES cells were injected into recipient blastocysts. The resulting chimeric animals were crossed to C57BL/6J females. Mice were crossed to B6;SJL-Tg(ACTFLPe)9205Dym/J to remove the neomycin cassette. Heterozygous mice were mated and offspring crossed to mixed C57BL/6 and 129/SvJ mice for several generations. Upon arrival, mice were bred to C57BL/6J for at least 1 generation to establish the colony.

Selected References

Maretzky T; Blobel CP; Guaiquil V. 2014. Characterization of oxygen-induced retinopathy in mice carrying an inactivating point mutation in the catalytic site of ADAM15. Invest Ophthalmol Vis Sci 55(10):6774-82PubMed: 25249606 MGI: J:217858

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Genetics

Adam15^tm2.1Bbl

Allele Symbol: Adam15^tm2.1Bbl

Allele Name	targeted mutation 2.1, Carl P Blobel
Allele Type	Targeted (Not Applicable)
Allele Synonym(s)	Adam15EA
Gene Symbol and Name	Adam15, a disintegrin and metallopeptidase domain 15 (metargidin)
Gene Synonym(s)
Strain of Origin	129P2/OlaHsd
Chromosome	3
Molecular Note	The targeting vector is designed to insert a E to A point mutation into the catalytic domain (exon 11) by site-directed mutagenesis. An FRT-flanked neomycin cassette is inserted downstream of exon 11. The mutation results in a A to C change at nucleotide 6829 altering the corresponding amino acid from glutamate to alanine. Flp-mediated recombination removed the FRT-flanked neo cassette.

Disease/Phenotype

Disease Terms

Research Areas By Phenotype

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

Cancer Research
- Genes Regulating Growth and Proliferation

Mammalian Phenotype Terms by Genotype

The following phenotype information is associated with a similar, but not exact match to this JAX^® Mice strain

Genotype: Adam15^tm2.1Bbl/Adam15^tm2.1Bbl
involves: 129/SvJ * 129P2/OlaHsd * C57BL/6J * SJL

neoplasm

decreased tumor growth/size
- size of tumors produced by heterotopically injected melanoma cells is reduced as compared to wild-type

abnormal tumor susceptibility
- 37.5% of mutant mice produce tumors as compared to 70.6% of wild-type mice

decreased tumor incidence
- number of tumors produced by heterotopically injected melanoma cells is reduced as compared to wild-type

vision/eye phenotype

abnormal retina inner limiting membrane morphology
- mice subjected to oxygen-induced retinopathy (OIR) exhibit an increase in the number of endothelial cell nuclei on the virtual side of the internal limiting membrane

abnormal retina morphology

retinal gliosis
- the number of tufts present in the retina is increased in response to oxygen-induced retinopathy

References

Maretzky T; Blobel CP; Guaiquil V. 2014. Characterization of oxygen-induced retinopathy in mice carrying an inactivating point mutation in the catalytic site of ADAM15. Invest Ophthalmol Vis Sci 55(10):6774-82PubMed: 25249606 MGI: J:217858

Additional - Adam15^tm2.1Bbl related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Standard PCR:Adam15
- Genotyping resources and troubleshooting
Breeding Considerations

While maintaining a live colony, these mice are bred as homoygotes.
- Additional Breeding and Husbandry Support
Citation
When using the Adam15 E>A mouse strain in a publication, please cite the originating article(s) and include MMRRC stock #37639 in your Materials and Methods section.

Animal Health Reports

Facility Barrier Level Descriptions

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

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. We do not guarantee breeding performance and therefore suggest that investigators order more than one breeding pair to avoid delays in their research.

Terms Of Use

General Terms and Conditions

See MMRRC for Additional Conditions of Distribution

Questions about Terms of Use

Licensing Information

Phone: 207-288-6470

Email: TechTran@jax.org

Also Known As:Adam15 E>A

Donating Investigator

Genetic overview

Research Applications

Detailed Description

Development

Selected References

Adam15tm2.1Bbl

Allele Symbol: Adam15tm2.1Bbl

Disease Terms

Research Areas By Phenotype

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

Mammalian Phenotype Terms by Genotype

Genotype: Adam15tm2.1Bbl/Adam15tm2.1Bblinvolves: 129/SvJ * 129P2/OlaHsd * C57BL/6J * SJL

neoplasm

vision/eye phenotype

References

Additional - Adam15tm2.1Bbl related

Genotyping Protocols

Breeding Considerations

Citation

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

The Jackson Laboratory's Genotype Promise

Terms Of Use

Licensing Information

Adam15^tm2.1Bbl

Allele Symbol: Adam15^tm2.1Bbl

Genotype: Adam15^tm2.1Bbl/Adam15^tm2.1Bbl
involves: 129/SvJ * 129P2/OlaHsd * C57BL/6J * SJL

Additional - Adam15^tm2.1Bbl related