B6.129-Pdk2^tm1Rhar/J

Stock number: 025634
Research areas: Metabolism Research, Research Tools

Description

This Pdk2 knockout strain is useful in studies of glucose homeostasis.

Detailed description

The predominantly expressed pyruvate dehydrogenase kinase isoform in skeletal muscle, isoenzyme 2, is encoded by the Pdk2 gene. Located in the mitrochondrial matrix, pyruvate dehydrogenase kinase, isoenzyme 2, inhibits the pyruvate dehydrogenase complex, and is involved in glucose metabolism regulation. These mice carry a knock out targeted mutation of the Pdk2 gene in which exon 1 and part of exon 2 are replaced by a PGK-NEO cassette. Mice that are homozygous for the targeted mutation are viable and fertile. No gene product (protein) is detected by Western blot analysis of mitochondria isolated from muscle tissue from homozygous animals. Homozygotes exhibit higher pyruvate dehydrogenase complex activity, and reduced non-fasting blood glucose levels when compared to wildtype controls.



When crossed with Pdk4 knock out mice (Stock No. 025633), the resulting double homozygotes exhibit lower blood glucose levels, fasting induced ketoacidosis and hypothermia, and increased pyruvate dehydrogenase complex activity.

Development

A targeting vector containing a PGK-NEO cassette was used to disrupt exon 1 and part of exon 2. The construct was electroporated into 129 derived R1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts. The resulting chimeric animals were tested for germline transmission. The mice were backcrossed to C57BL/6J for 8 generations. Upon arrival at The Jackson Laboratory, the mice were crossed to C57BL/6J (Stock No. 000664) at least once to establish the colony.

Allele

Symbol: Pdk2^tm1Rhar
Name: targeted mutation 1, Robert A Harris
MGI accession ID: MGI:3521813
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Pdk2
Marker name: pyruvate dehydrogenase kinase, isoenzyme 2
Chromosome: 11
Strain of origin: (129X1/SvJ x 129S1/Sv)F1-Kitl⁺
Molecular note: Exon 1 and part of exon 2 were deleted by insertion of a neomycin resistance cassette. Western blot analysis confirmed the absence of translation product.