TET family proteins are dispensable for the structure and function of dopamine neurons in health and Parkinson’s disease

Abstract

DNA undergoes demethylation via the oxidation of 5-methylcytosine (5mC), which is mediated by the Ten Eleven Translocation (TET) family of proteins. Notably, 5hmC is highly enriched in the brain than other tissues, the level of which is dynamically regulated during development, aging, and in brain disorders. In addition, accumulating evidence has recently revealed that 5-hmC and TETs play a significant role in synaptic functions, anxiety, addiction, and cognition in several brain regions. Furthermore, TET enzymes have turned out to be essential for diverse types of neurons in health and brain disorders. In this study, by generating triple knockout (TKO) mice of TET family proteins (TET1, 2, and 3) selectively in dopamine (DA) neurons, we investigated the functional roles of TET proteins in the structure and the function of DA neurons, which are pivotal for voluntary movement, reward-related behaviors, and motivation. Here we unexpectedly show that triple knockout (TKO) of all three TET proteins in dopamine (DA) neurons did not lead to critical alterations of neuronal structure and function in normal and pathological mouse brain. Thus, contrary to the previous reports, TET family enzymes may be dispensable for the structure and function of neurons in health and disease.