B6(SJL)-Pik3cb^tm1.1Jdo/J

Stock number: 025930
Strain synonyms: Pik3cb RBD
Research areas: Cancer Research, Cell Biology Research, Immunology, Inflammation and Autoimmunity Research

Description

Cells from these Pik3cb RBD mutant mice show reduced phosphoinositide 3-kinase (PI3K) activity and defective chemotaxis.

Detailed description

Pik3cb (phosphatidylinositol 3-kinase, catalytic, beta polypeptide; also called p110β) is implicated in G-protein-coupled receptor (GPCR) signaling, PTEN-loss-driven cancers, and thrombocyte function. RAC1 and CDC42 (from the RHO subfamily of small GTPases) bind and activate PIK3CB via its RAS binding domain (RBD), but PIK3CB does not bind RAS.

S205D and K224A point mutations were introduced to the catalytic subunit of the mouse Pik3cb gene, disrupting interactions with Ras family GTPases. In vitro, the basal lipid kinase activity of purified recombinant protein is indistinguishable from its wildtype counterpart. Cells from mice carrying mutations in the PIK3CB RBD show reduced phosphoinositide 3-kinase (PI3K) activity and defective chemotaxis. Mouse embryonic fibroblasts (MEFs) from these mice show reduced PI3K and these mice are resistant to bleomycin-induced lung fibrosis.

Homozygotes are smaller than their wildtype littermates both as newborns and as adults.

Development

S205D (AGT->GAT) and K224A (AAA->GCA) point mutations were introduced to the catalytic subunit of the gene and an FRT-flanked neomycin selection cassette was inserted in intron 6. The targeting construct was introduced to C57BL/6-derived embryonic stem cells. The neomycin selection cassette was excised through crosses with Tg(ACTFLPe)9205Dym deleter mice, leaving a single FRT site in intron 6/7, which may be used for PCR genotyping. This strain was backcrossed to C57BL/6J for at least 8 generations by the donating laboratory.

Allele

Symbol: Pik3cb^tm1.1Jdo
Name: targeted mutation 1.1,Julian Downward
MGI accession ID: MGI:5646522
Generation method: Targeted
Attributes: Not Specified
Synonyms: p110beta-RBD-DM
Marker symbol: Pik3cb
Marker name: phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta
Marker synonyms: 1110001J02Rik; P110BETA; PI3K; PI3KBETA; PIK3C1
Chromosome: 9
Strain of origin: C57BL/6
Expressed genes: Pik3cb,phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta,mouse, laboratory
Site of expression: Mouse embryonic fibroblasts.
Molecular note: S205D (AGT->GAT) and K224A (AAA->GCA) point mutations were introduced to the catalytic subunit of the gene and an FRT-flanked neomycin selection cassette was inserted in intron 6. The neomycin selection cassette was excised through crosses with Tg(ACTFLPe)9205Dym deleter mice, leaving a single FRT site in intron 6/7.