B6(SJL)-Pla2g6^{tm1c(EUCOMM)Hmgu}/TurkMewJ

Stock number: 027806
Product name: Pla2g6 flox
Research areas: Neurobiology Research, Research Tools

Description

Exons 6 through 8 of the Pla2g6, phospholipase A2, group VI, gene is flanked by loxP sites in this conditional iPLA₂β mutant strain. This strain may be useful for generating conditional mutations in applications related to the study of neurodegeneration, peripheral neuropathies and neuronal regeneration after injury.

Detailed description

The calcium-independent A2 phospholipase encoded by the Pla2g6 gene is involved in membrane phospholipid remodeling, fatty acid oxidation, as well as cell growth, signal transduction and cell death. Mutations in this gene have been associated with neurodegeneration, peripheral neuropathies and infantile neuroaxonal dystrophy. These mice possess loxP sites on either side of 6 through 8 of the targeted gene. Mice that are homozygous for this allele are viable and fertile. When these mutant mice are bred to mice that express Cre recombinase, resulting offspring will have 6 through 8 deleted in the cre-expressing tissues. Removal of the floxed sequence creates a null allele, as the truncated mRNA that is produced is eliminated by nonsense mediated decay.

Development

C57BL/6N-A^tm1Brd-derived JM8A3.N1 embryonic stem (ES) cells (HEPD0731_2_G05 or HEPD0731_2_G07) containing a targeted mutation of the Pla2g6, phospholipase A2, group VI, gene were obtained from The European Conditional Mouse Mutagenesis Program (EUCOMM). The mutant allele has, from 5’ to 3’, a FRT site, an En2 splice acceptor cassette containing IRES, β-galactosidase and polyA sequence, a loxP site, human beta-actin promoter, SV40 polyA, a second FRT site, and a second loxP site inserted upstream of exon 6. A third loxP-site is inserted downstream of exon 8. Correctly targeted ES cells were injected into blastocysts. The resulting chimeric animals were tested for germline transmission. The mice were then crossed to FLP deleter mice (Stock No. 005703) to excise the FRT flanked En2 splice acceptor and NEO cassettes. Upon arrival, sperm was cryopreserved. To establish our live colony, an aliquot of frozen sperm was used to fertilize C57BL/6J oocytes (Stock No. 000664).

Allele

Symbol: Pla2g6^{tm1c(EUCOMM)Hmgu}
Name: targeted mutation 1c, Helmholtz Zentrum Muenchen GmbH
MGI accession ID: MGI:5754997
Generation method: Targeted
Attributes: Conditional ready (e.g. floxed); No functional change
Marker symbol: Pla2g6
Marker name: phospholipase A2, group VI
Marker synonyms: CaI-PLA2; GVI; GVI PLA2; INAD1; iPla2; iPLA2beta; iPLA2-beta; IPLA2-VIA; NBIA2; NBIA2A; NBIA2B; PARK14; PLA2; PNPLA9
Chromosome: 15
Strain of origin: C57BL/6N-A^tm1Brd
Molecular note: The mutant allele has, from 5' to 3', an FRT site, an En2 splice acceptor cassette containing IRES, beta-galactosidase and polyA sequence, a loxP site, human beta-actin promoter, SV40 polyA, a second FRT site, and a second loxP site inserted upstream of exon 6. A third loxP-site is inserted downstream of exon 8. Flp-mediated recombination removed the FRT-flanked neo cassette and En2 splice acceptor leaving exons 6 through 8 floxed. Further information on targeting strategies used for this and other IKMC alleles can be found at http://www.informatics.jax.org/mgihome/nomen/IKMC_schematics.shtml.