Parkinson’s disease (PD) is characterized by an extensive loss of dopaminergic neurons (DN) in the substantia nigra pars compacta (SNc) and their terminals in the striatum. Lowered glutathione content has been found in the SNc of patients with pre-symptomatic PD. We recently reported that inhibition of glutamate cysteine ligase (GCL), i.e. the heterodimeric enzyme that catalyzes the first rate-limiting step in glutathione biosynthesis, leads to neurodegeneration in vitro either in the presence or in the absence of astroglial cells in co-culture (1). To assess whether this effect occurs in vivo, we have now designed a temporally regulated DNA construct to inhibit GCL catalytic subunit in a tissue-specific manner. The 9 kb tyrosine hydroxilase rat promoter (2) has been bound to a tamoxifen-inducible form of Cre recombinase (3). In the presence of tamoxifen, Cre promotes the recombination of a Lox-flanked region that contains the green fluorescent protein (GFP), an H1 promoter and a short-hairpin RNA (shRNA) targeted against GCL. This temporally regulated recombination, which can be detected by GFP fluorescence, leads to the expression of a GCL shRNA specifically confined to DN. The implementation of this system for the generation of transgenic mice thus represents a novel tool to investigate the mechanism of DN death by oxidative stress in a PD-like model, as well as for the search of novel therapeutic strategies against this devastating disease