STOCK Ank1^tm1.1Mnr/J

Stock number: 036512
Product name: Ank1^F
Research areas: Neurobiology Research, Research Tools

Description

Exons 26 and 27 of the mouse Ank1 (ankyrin 1, erythroid; also called neuronal AnkR) gene are flanked by loxP sites in these Ank1^F conditional mutant mice. Cre recombinase-mediated excision of the floxed region results in a knock-out allele useful in studies of ankyrin functionality.

Detailed description

Neuronal ankyrins cluster and link membrane proteins to the actin and spectrin-based cytoskeleton. Neuronal Ankyrin-R (also called AnkR; encoded by Ank1, ankyrin 1, erythroid) is highly enriched in PV⁺ fast-spiking inhibitory interneurons in both mice and humans.

Exons 26 and 27 of the mouse Ank1 gene, upstream of the spectrin binding domain, are flanked by loxP sites in these Ank1^F conditional mutant mice. Cre recombinase-mediated excision of the floxed region results in a frame-shift mutation that generates a premature stop codon in exon 28. Directed, tissue-specific knock-out of Ank1 expression allows for an exploration of AnkR function in the brain while avoiding complications of anemia due to a loss of AnkR from red blood cells.

Crosses with Dlx5/6-Cre mice (Stock No. 008199) create an AnkR knock-out in forebrain interneurons, as determined by immunoblot of brain homogenates and immunostaining of forebrain sections. This reduces and disrupts perineuronal nets (PNNs), decreases anxiety-like behaviors, and changes the intrinsic excitability and firing properties of Pv⁺ fast-spiking interneurons. A dramatic reduction in Kv3.1b K⁺ channels accompanies these changes.

AnkR expression can be more broadly knocked out in the nervous system through crosses with Nestin-Cre mice (Stock No. 003771). This results in in Purkinje cell degeneration and cerebellar dysfunction.

It is expected that loss of AnkR from eryththrocytes would result in severe hemolytic anemia.

Development

An FRT-IRES-GFP-loxP-NeoStop-FRT-loxP cassette was introduced to intron 25 and a loxP site was placed in intron 27 of the mouse Ank1 gene via homologous recombination in embryonic stem (ES) cells. The segment flanked by FRT sites was excised with Flp recombinase, leaving exons 26 and 27 flanked by loxP sites. Resultant mice were backcrossed to C57BL/6J mice (Stock No. 000664) for at least 4 generations by the donating laboratory.

Allele

Symbol: Ank1^tm1.1Mnr
Name: targeted mutation 1.1, Matthew N Rasband
MGI accession ID: MGI:6717196
Generation method: Targeted
Attributes: Conditional ready (e.g. floxed)
Synonyms: Ank1^F
Marker symbol: Ank1
Marker name: ankyrin 1, erythroid
Marker synonyms: ANK; Ank-1; ankyrin-1; pale; SPH1; SPH2
Chromosome: 8
Strain of origin: Not Specified
Molecular note: An FRT-IRES-GFP-loxP-NeoStop-FRT-loxP cassette ws introduced to intron 25 and a loxP site was placed in intron 27. Flp-mediated recombination removed the FRT-flanked neo cassette leaving exons 26 and 27 floxed.