B6.Cg-Akap11^tm1.2Jsco/J

Stock number: 028922
Product name: AKAP220 knockout
Research areas: Cell Biology Research, Developmental Biology Research, Internal/Organ Research, Metabolism Research, Neurobiology Research

Description

Exons 6 and 7 of the mouse Akap11 gene have been deleted to create a knockout allele. Homozygous knockout mice exhibit reduced body size, reduced locomotion, elevated anxiety, and changes in water homeostasis.

Detailed description

A-Kinase Anchoring Protein 220 (AKAP220) protein, encoded by the Akap11 (A kinase (PRKA) anchor protein 11) gene, is a ubiquitously-expressed vesicular- and membrane-associated anchoring protein. It has been implicated in the modulation of cytoskeletal signaling events, and is integral to water reabsorption processes in the kidney.

Exons 6 and 7 of the mouse Akap11 gene have been excised in this knockout allele. Protein is reported to be undetectable in all tested tissues from homozygous animals. Mice homozygous for the null allele have reduced body size throughout life (both males and females). They also display reduced locomotion and elevated anxiety behavior in open field test. Phenotypic analysis of the kidney collecting duct reveals mislocalization of aquaporin-2 (AQP2) water channels and disrupted apical actin in knockout mice, leading to changes in water homeostasis.

Development

A loxP site and FRT-flanked neomycin cassette were introduced to intron 5 of the mouse Akap11 gene and a loxP site was placed in intron 7 via homologous recombination in (129S6/SvEvTac x C57BL/6)F1-derived G4 embryonic stem (ES) cells. A resultant chimeric male was bred to C57BL/6J females. The neomycin cassette was excised through crosses with B6(C3)-Tg(Pgk1-FLPo)10Sykr/J animals (see Stock No. 011065), leaving exons 6 and 7 flanked by loxP sites. Animals were backcrossed to C57BL/6J for 6 generations by the donating laboratory. Mice were crossed with EIIa-cre mice (see Stock No. 003724) to excise exons 6 and 7 in the germline.

Allele

Symbol: Akap11^tm1.2Jsco
Name: targeted mutation 1.2, John D Scott
MGI accession ID: MGI:5751858
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Akap11
Marker name: A kinase (PRKA) anchor protein 11
Chromosome: 14
Strain of origin: (129S6/SvEvTac x C57BL/6NCrl)F1
Molecular note: A loxP site and FRT-flanked neomycin cassette are introduced into intron 5 followed by a loxP site placed in intron 7. Flp-mediated recombination removed the FRT-flanked neo cassette. Cre-mediated recombination removed exons 6 and 7. Western blot anaylsis on nine tissues confirmed that no protein was expressed in mutant mice.