B6.Cg-Birc3^tm1Jda/J

Stock number: 023316
Product name: c-IAP2^H570A
Research areas: Immunology, Inflammation and Autoimmunity Research, Research Tools

Description

These c-IAP2^H570A mice contain a H570A mutation in exon 9 the Birc3 gene resulting in a lack of E3 ubiquitin-protein ligase activity in B and T lymphocytes.

Detailed description

These c-IAP2^H570A mice contain the amino acid mutation H570A in exon 9 of the baculoviral IAP repeat-containing 2 (Birc3) gene. C-IAP2 (Cellular Inhibitor of Apoptosis 2) 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 H570A mutation is in the RING domain, inactivating the E3 ubiquitin-protein ligase activity. c-IAP2^H570A protein levels are increased due to lack of autoubiquitination and degradation and exert a dominant negative effect on c-IAP1 E3 activity. As a result, c-IAP2^H570A cells have constitutively active non-canonical NF-kappa-B resulting in high levels of p52 at rest. c-IAP2^H570A mice have enlarged gut associated lymphoid tissue (GALT), marginal zone B cell hyperplasia, increased B cell survival, and T cell-costimulation independence.

Development

A targeting construct was designed to insert a loxP-flanked neomycin (neo) resistance cassette downstream of exon 9 of the baculoviral IAP repeat-containing 3 (Birc3) gene. A point mutation was introduced in exon 9, encoding a RING domain, resulting in the H570A 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 offspring were bred to C57BL/6 mice for at least six generations. Upon arrival at The Jackson Laboratory, mutant mice were bred to C57BL/6NJ mice (Stock No. 005304) for at least one generation to establish the colony.

Allele

Symbol: Birc3^tm1Jda
Name: targeted mutation 1, Jonathan D Ashwell
MGI accession ID: MGI:4887220
Generation method: Targeted
Attributes: Not Applicable
Marker symbol: Birc3
Marker name: baculoviral IAP repeat-containing 3
Chromosome: 9
Strain of origin: 129 x C57BL/6
Molecular note: Exon 9 was replaced with one in which nucleotide substitutions result in the amino acid substitution of alanine for histidine at position 570 (H570A). A floxed neo cassette was inserted downstream of the modified exon 9.