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An obsession with producing and validating models (face, construct, predictive validity) has led many of us down a deep rabbit hole, thinking about models instead of mechanisms. Advances in the human genetics and neurobiology of brain disorders create exciting new opportunities, but only if we can get back to basics.
Glial cell line-derived neurotrophic factor (GDNF) is in clinical trials for treating Parkinson's disease. However, endogenous GDNF function in brain catecholaminergic neurons has remained controversial. The authors utilized three complementary conditional knock-out approaches during development and adulthood and found that GDNF is not required for the maintenance of the catecholaminergic neurons in mice.
