Exon 2 of the mouse Akap5 gene is flanked by loxP sites. Cre-mediated excision of the exon creates a null allele, useful in studies of synaptic transmission, memory and insulin sensitivity.
John D. Scott, University of Washington
A-Kinase Anchoring Proteins (AKAPs) ensure the fidelity of second messenger signaling events by directing protein kinases and phosphatases toward their preferred substrates. AKAP150 (Akap5, A kinase (PRKA) anchor protein 5) brings protein kinase A (PKA), the calcium/calmodulin dependent phosphatase PP2B and protein kinase C (PKC) to postsynaptic membranes where they facilitate the phosphorylation dependent modulation of certain ion channels.
The single coding exon of Akap5 (exon2) was flanked by loxP sites in this targeted mutant strain. Cre-mediated excision of the floxed region creates a null allele.
Homozygous knock-out mice (see Stock No. 026692) developed through crosses with CMV-cre have impaired motor coordination and strength, harbor deficits in spatial memory retention, and show reduced anxiety. They also secrete less insulin from β-cells, yet display improved glucose handling because of increased insulin sensitivity in target tissues.
Conditional ablation of AKAP5 from insulin-expressing cells through crosses with Ins2-cre mice (see Stock No. 003573) attenuates insulin secretion in a specific manner but importantly does not alter insulin sensitivity in peripheral tissues.
LoxP sites were introduced on either side of the single coding exon (exon 2) and an FRT-flanked neomycin cassette was placed downstream via homologous recombination in 129SvEv-derived embryonic stem cells. Resultant chimeric mice were crossed with FLPeR mice (see Stock No. 009086) to remove the neomycin resistance cassette. This strain was backcrossed to C57BL/6J for more than 12 generations by the donating laboratory.
|Allele Name||targeted mutation 1, John D Scott|
|Allele Type||Targeted (Conditional ready (e.g. floxed), No functional change)|
|Gene Symbol and Name||Akap5, A kinase (PRKA) anchor protein 5|
|Strain of Origin||129S/SvEv|
|Molecular Note||The loxP sites were introduced into both 5' and 3' of a single coding exon of the gene. A FRT flanked neo cassette was also introduced at down stream of the exon by homologous recombination in ES cells, and after germline transmission, removed by crossing with Flp expressing mice leaving loxP flanked coding exon.|
Homozygotes and heterozygotes are viable and fertile.
When using the B6.129S-Akap5tm1Jsco/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #026694 in your Materials and Methods section.