Behavioral abnormalities and Parkinson’s-like histological changes resulting from Id2 inactivation in mice

SUMMARY

Characterizing dopaminergic neuronal development and function in novel genetic animal models might uncover strategies for researchers to develop disease-modifying treatments for neurologic disorders. Id2 is a transcription factor expressed in the developing central nervous system. Id2 ^−/− mice have fewer dopaminergic neurons in the olfactory bulb and reduced olfactory discrimination, a pre-clinical marker of Parkinson’s disease. Here, we summarize behavioral, histological and in vitro molecular biological analyses to determine whether midbrain dopaminergic neurons are affected by Id2 loss. Id2 ^−/− mice were hyperactive at 1 and 3 months of age, but by 6 months showed reduced activity. Id2 ^−/− mice showed age-dependent histological alterations in dopaminergic neurons of the substantia nigra pars compacta (SNpC) associated with changes in locomotor activity. Reduced dopamine transporter ( DAT) expression was observed at early ages in Id2 ^−/− mice and DAT expression was dependent on Id2 expression in an in vitro dopaminergic differentiation model. Evidence of neurodegeneration, including activated caspase-3 and glial infiltration, were noted in the SNpC of older Id2 ^−/− mice. These findings document a novel role for Id2 in the maintenance of midbrain dopamine neurons. The Id2 ^−/− mouse should provide unique opportunities to study the progression of neurodegenerative disorders involving the dopamine system.