Exon 2 of the mouse Akap5 gene was excised to create a null allele. Homozygotes 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.
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.
Exon 2 of the mouse Akap5 gene has been deleted to create a knockout allele in these targeted mutant mice. Homozygous mice have impaired motor coordination and strength, harbor deficits in spatial memory retention, and show reduced anxiety. Loss of AKAP5 in sympathetic cervical ganglion (SCG) neurons reduces muscarinic suppression of inhibitory M currents (K+ conductance) and provides these animals with a measure of resistance to seizures induced by the non-selective muscarinic agonist pilocarpine. AKAP5 null mice secrete less insulin from β-cells, yet display improved glucose handling because of increased insulin sensitivity in target 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. Further crosses with a Cre deleter strain (see Stock No. 003724) excised the floxed exon. This strain was backcrossed to C57BL/6J for 13 generations by the donating laboratory.
|Allele Name||targeted mutation 1.1, John D Scott|
|Allele Type||Targeted (Null/Knockout)|
|Allele Synonym(s)||AKAP150-; Akap5tm1.1Jscoe|
|Gene Symbol and Name||Akap5, A kinase (PRKA) anchor protein 5|
|Strain of Origin||129S/SvEv|
|Molecular Note||The loxP flanked coding exon from Akap5tm1Jscoe was removed by crossing with Cre deleter mice, Tg(EIIa-cre)C5379Lmgd. FLP mediated recombination removed the FRT-flanked neo cassette. Immunoblots and immunohistochemistry confirmed absence of protein in brain. This is a null allele.|
Homozygotes and heterozygotes are viable and fertile.
When using the B6.129S(FVB)-Akap5tm1.1Jsco/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #026692 in your Materials and Methods section.