Cells from these Pik3cb RBD mutant mice show reduced phosphoinositide 3-kinase (PI3K) activity and defective chemotaxis.
Julian Downward, Francis Crick Institute
Genetic Background | Generation |
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Allele Type | Gene Symbol | Gene Name |
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Targeted (Not Specified) | Pik3cb | phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta |
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.
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.
Expressed Gene | Pik3cb, phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta, mouse, laboratory |
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Site of Expression | Mouse embryonic fibroblasts. |
Allele Name | targeted mutation 1.1,Julian Downward |
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Allele Type | Targeted (Not Specified) |
Allele Synonym(s) | p110beta-RBD-DM |
Gene Symbol and Name | Pik3cb, phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta |
Gene Synonym(s) | |
Expressed Gene | Pik3cb, phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta, mouse, laboratory |
Site of Expression | Mouse embryonic fibroblasts. |
Strain of Origin | C57BL/6 |
Chromosome | 9 |
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. |
Heterozygous and homozygotes are viable and fertile. Homozygotes are smaller than their wildtype littermates both as newborns and as adults.
When using the B6(SJL)-Pik3cbtm1.1Jdo/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #025930 in your Materials and Methods section.
Facility Barrier Level Descriptions
Service/Product | Description | Price |
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Heterozygous or wildtype for Pik3cb<tm1.1Jdo> |
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