Excision of exon 7 was achieved using the Cre-LoxP recombination system. The deletion of exon 7 leads to a frame shift, introducing a premature stop codon in exon 8.
The animals described here are homozygous knockout mice.
Endogenous Parkin: No
Corresponding human genotype: The deletion or duplication of exons 7 has been found to be associated with Parkinson’s disease.
Targeted gene: Parkin
References: Von Coelln 2004
The absence of Parkin expression confirmed by western blot.
2 and 12-18 months: No significant degeneration of TH-positive neurons or fibres can be observed in the SN or the striatum of the KO mice. A significant decrease in the number of TH positive neurons can be observed in the locus coeruleus of the KO animals.
12-18 months: Striatal levels of DA and its major metabolites (DOPAC, HVA) are similar in KO and wild type animals.
There is significant reduction of norepinephrine in the olfactory bulb and spinal cord of the transgenic animals compared to wild type mice.
12-18 months: No inclusions (alpha-synuclein, ubiquitin, thioflavin S) are observed in the midbrain, striatum, cortex, olfactory bulb and brainstem.
3 and 24 months: Performances of KO mice in the open field and on the accelerated rotarod are comparable to those of wild type animals. The acoustic startle response is dramatically decreased in parkin KO mice.
Response to dopaminergic treatment
12-18 months: No changes in glial activation (astrocyte immunostaining) is observed in KO mice compared to wild type animals.