The Pdk4 gene encodes pyruvate dehydrogenase kinase, isoenzyme 4, a mitochondrial protein containing a histidine kinase domain. Located in the mitrochondrial matrix, pyruvate dehydrogenase kinase, isoenzyme 4, inhibits the pyruvate dehydrogenase complex, and is involved in glucose metabolism regulation. These mice carry a knock out targeted mutation of the Pdk4 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 muscle tissue from homozygotes.
Homozygotes exhibit slightly improved glucose tolerance and greater insulin sensitivity when compared to wildtype controls. On a high fat diet, homozygotes display improved glucose tolerance and lower body weight than wildtype. Increased myocardial pyruvate dehydrogenase complex activity in null mice protects against ischaemia/reperfusion injury.
When crossed with Pdk2 knock out mice (Stock No. 025634), the resulting double homozygotes exhibit lower blood glucose levels, fasting induced ketoacidosis and hypothermia, and increased pyruvate dehydrogenase complex activity.
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 Name||targeted mutation 1, Robert A Harris|
|Allele Type||Targeted (Null/Knockout)|
|Gene Symbol and Name||Pdk4, pyruvate dehydrogenase kinase, isoenzyme 4|
|Strain of Origin||(129X1/SvJ x 129S1/Sv)F1-Kitl+|
|Molecular Note||Exon 1 and part of exon 2 were replaced with a PGK-neomycin resistance cassette. Western blot analysis confirmed the absence of translation product.|
When maintaining a live colony, these mice can be bred as homozygotes.
When using the B6.129-Pdk4tm1Rhar/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #025633 in your Materials and Methods section.