In vivo models of Parkinson’s disease – Mammalian models



Mutations in DJ-1 have been identified in autosomal recessive forms of early-onset familial PD. These mutations involve large deletions in exon sequences or promoter region as well as missense mutations that all lead to loss of function of the DJ-1 protein (Bonifati et al., 2003). A functional DJ-1 protein therefore seems to be involved in neuroprotective mechanisms that protect neurons from cell death.

DJ-1 is a ubiquitously expressed and highly conserved dimeric protein. It is implicated in many cellular processes, such as homeostatic control of reactive oxygen species and transcription regulation, and has a major function in neuronal protection against oxidative stress.

DJ-1 possesses three cysteine residues from which one (C106) is highly conserved in mammals. This residue seems to determine the “oxidative stress sensor” function of the protein, and is essential for the antioxidant properties of DJ-1.

The precise physiological role of DJ-1 still needs to be elucidated. A recent review (Biosa et al, 2017), discusses the possible mechanisms involved in the neuroprotective function of DJ-1.

SpeciesPINK1MutationGenotypeNeurodegeneration (Y/N)Link
MouseGermline inactivationExon 2 deletionDJ-1-/-N/Y (retinas)mDJ-1 KO
MouseGermline inactivationExon 3-5 deletionDJ-1-/-Y (unilateral)mDJ-1KO/ 1
MouseGermline inactivationExon 2-3 deletionDJ-1-/-NmDJ-1 KO/2
MouseGermline inactivationExon 7 deletionDJ-1-/-N (increased DA levels)mDJ-1 KO/3
RatGermline inactivationExon 5 deletionDJ-1-/-Y (unilateral)rDJ-1 KO

Updated 25-04-2018