STOCK Adam15^tm2.1Bbl/Mmjax

Stock number: 027228
Product name: Adam15 E>A
Research areas: Cancer Research

Description

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.

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.

Allele

Symbol: Adam15^tm2.1Bbl
Name: targeted mutation 2.1, Carl P Blobel
MGI accession ID: MGI:5616076
Generation method: Targeted
Attributes: Not Applicable
Marker symbol: Adam15
Marker name: a disintegrin and metallopeptidase domain 15 (metargidin)
Chromosome: 3
Strain of origin: 129P2/OlaHsd
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.