These mice contain a H582A mutation in exon 7 of the Birc2 gene, resulting in a lack of E3 ubiquitin-protein ligase activity in B and T cells.
Jonathan D Ashwell, Nat Cancer Inst/Nat Inst Health NCI/NIH
These c-IAP1H582A mice contain the amino acid mutation H582A in exon 7 of the baculoviral IAP repeat-containing 1 (Birc2) gene. c-IAP1 (Cellular Inhibitor of Apoptosis 1) acts as an E3 ubiquitin-protein ligase which regulates non-canonical NF-kappa-B signaling, caspase activity, apoptosis, inflammatory signaling and immunity, mitogenic kinase signaling, cell proliferation, cell invasion, and metastasis. This H582A mutation is in the RING domain, inactivating the E3 ubiquitin-protein ligase activity. As a result, c-IAP1H582A cells have high levels of c-IAP2. c-IAP2 compensate for the lack of c-IAP1 E3 activity in regulating non-canonical NF-kappa-B in B cells but not completely in T cells.
A targeting construct was designed to insert a loxP- and frt-flanked neomycin (neo) resistance cassette downstream of exon 7 of the baculoviral IAP repeat-containing 2 (Birc2) gene. A point mutation was introduced in exon 7, encoding a RING domain, resulting in the H582A mutation. This targeting construct was electroporated into 129 x C57BL/6 embryonic stem (ES) cells and correctly targeted ES cells were injected into blastocysts. The resulting chimeric males were bred to beta-actin-cre expressing transgenic mice to remove the neo cassette, and offspring were crossed to remove the cre-expressing transgene. c-IAP1H582A offspring were bred to C57BL/6J mice for at least 6 generations. Upon arrival at The Jackson Laboratory, mutant mice were bred to C57BL/6J mice (Stock No. 000664) for at least one generation to establish the colony.
|Allele Name||targeted mutation 2.1, Jonathan D Ashwell|
|Allele Type||Targeted (Not Specified)|
|Allele Synonym(s)||c-IAP2H570A; c-IAP2ki|
|Gene Symbol and Name||Birc2, baculoviral IAP repeat-containing 2|
|Strain of Origin||129 x C57BL/6|
|Molecular Note||A targeting construct was designed to insert a loxP- and frt-flanked neomycin (neo) resistance cassette downstream of exon 7. A point mutation was introduced in exon 7, encoding a RING domain, resulting in an H582A mutation. Cre-mediated recombination removed the neo cassette.|
When maintaining a live colony, homozygous mice may be bred together.
When using the B6.Cg-Birc2tm2.1Jda/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #023315 in your Materials and Methods section.