These Pink1 knockout mice exhibit reduced mean evoked dopamine overflow, altered dopamine signaling, and have applications in studies related to Parkinson's disease.
Jie Shen, Harvard Med Sch/Brigham Women's Hosp
These Pink1 (PTEN induced putative kinase 1) knockout mice have exons 4 through 7 deleted, disrupting most of the kinase domain and producing a nonsense mutation at the start of exon 8 due to a reading frame shift. Missense mutations in the PINK1 gene cause autosomal-recessive Parkinson's disease. PINK1 loss of function results in mitochondrial dysfunction, increased reactive oxygen species production and calcium homeostasis imbalance. Homozygous mutant mice are viable and fertile. No Pink1 mRNA is detected by Northern blot analysis in brain tissue from homozygotes. Evoked release of striatal dopamine and catecholamine, and catecholamine release by adrenal chromaffin cells is decreased in homozygotes. Dopamine levels in the striatum, dopaminergic neuron number, dopamine synthesis and dopamine receptor number are not altered. Homozygotes exhibit impaired induction of long-term potentiation and long-term depression at corticostriatal synapses. No nigrostriatal neurodegeneration is detected in homozygous mice 9 months of age. Homozygotes are more sensitive to metabotropic glutamate (mGlu) receptor agonist than wildtype controls.
A targeting vector containing a PGK-NEO cassette was used to disrupt exons 4 through 7. The construct was electroporated into 129S4/SvJae derived J1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts. The resulting chimeric animals were crossed to generate homozygotes. The mice were then backcrossed to C57BL/6J for 7 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, Jie Shen|
|Allele Type||Targeted (Null/Knockout)|
|Gene Symbol and Name||Pink1, PTEN induced putative kinase 1|
|Strain of Origin||129S4/SvJae|
|Molecular Note||Exons 4-7 were replaced with a pgk-neo cassette via cre mediated recombination, thereby removing the majority of the kinase domain and creating a nonsense mutation at the beginning of exon 8. Northern blot confirmed absence of transcript in mutants.|
When maintaining a live colony, these mice can be bred as homozygotes.
When using the Pink1- mouse strain in a publication, please cite the originating article(s) and include JAX stock #017946 in your Materials and Methods section.
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