B6.Cg-Dpp6^tm1.1Dahn/J

Stock number: 017972
Research areas: Neurobiology Research

Description

These dipeptidylpeptidase 6 (Dpp6) knockout mice exhibit a loss of A-type K⁺ current in distal dendrites and may be useful in studies of dendritic function and potassium currents.

Detailed description

The transmembrane auxillary subunit, dipeptidylpeptidase 6 (Dpp6), is expressed in dendrites of CA1 pyramidal neurons and other areas of the brain. It is an auxiliary subunit of potassium channels containing Kv4 (Kcnd) pore forming subunits. DPP6 regulates the expression of Kv4.2 (Kcnd2) as well as the subcellular pattern of expression and properties of Kv4-containing A-type K⁺ channels. CA1 pyramidal neuron apical dendrites in mice homozygous for this null allele exhibit a loss of A-type K⁺ current in distal dendrites, an increased depolarizing shift in the inactivation curve of proximal dendrites, and a slower recovery from inactivation. These effects result in hyperexcitable dendrites with enhanced backpropagation of action potentials and long term potentiation. Mice that are homozygous for the targeted mutation are viable, fertile, normal in size. This mutant mouse strain may be useful in studies of dendritic function, potassium currents and their relation to behavior.

Development

A targeting vector was designed to insert a loxP site upstream of exon 2 followed by a FRT-flanked neomycin resistance (neo) cassette, and a second loxP site downstream of exon 2 of the dipeptidylpeptidase 6 (Dpp6) gene. The construct was electroporated into C57BL/6-derived Bruce 4 embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts and the resulting chimeric mice were bred to C57BL/6 mice. The donating investigator reported that mice were crossed to a Cre deleter strain on a C57BL/6 background (see SNP note below) to remove exon 2 and the neo cassette. Upon arrival at The Jackson Laboratory, mice were bred to C57BL/6J inbred mice (Stock No. 000664) for at least one generation to establish the colony.

A 32 SNP (single nucleotide polymorphism) panel analysis, with 27 markers covering all 19 chromosomes and the X chromosome, as well as 5 markers that distinguish between the C57BL/6J and C57BL/6N substrains, was performed on the rederived living colony at The Jackson Laboratory Repository. While the 27 markers throughout the genome suggested a C57BL/6 genetic background, 4 of 5 markers that determine C57BL/6J from C57BL/6N were found to be segregating. These data suggest the mice sent to The Jackson Laboratory Repository were on a C57BL/6N genetic background.

Allele

Symbol: Dpp6^tm1.1Dahn
Name: targeted mutation 1.1, Dax A Hoffman
MGI accession ID: MGI:5302080
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Dpp6
Marker name: dipeptidylpeptidase 6
Chromosome: 5
Strain of origin: B6.Cg-Thy1^a
Molecular note: A loxP site was inserted upstream of exon 2. An FRT-flanked neo cassette with a 3' loxP site was inserted downstream of exon 2. Cre-mediated recombination removed exon 2 and the neo cassette. Immunohistochemistry confirmed the absence of protein expression in the brain.