Conditional ablation of protein tyrosine phosphatase receptor U in midbrain dopaminergic neurons results in reduced neuronal size

Abstract

Protein tyrosine phosphatase receptor U (PTPRU) is involved in midbrain patterning during early stages of development and is continuously expressed in the adult midbrain areas where dopaminergic neurons reside in. However, whether PTPRU is also involved in the maintenance and survival of midbrain dopaminergic (mDA) neurons during the late stages of development or in the adult midbrain remains largely unknown. In the present study, Ptpru was ablated by crossing a floxed Ptpru mouse strain with tyrosine hydroxylase (TH)-Cre mice that express Cre recombinase in postmitotic mDA neurons. Conditional ablation of Ptpru in postmitotic mDA neurons resulted in a reduction of somatic and nuclear size in adulthood. However, TH-immunoreactivity of Ptpru-ablated mDA neurons and their projections to the striatum appeared undisturbed. We also investigated the maintenance of several mDA neuronal markers following Ptpru ablation and found no significant changes. Taken together, these findings suggest that PTPRU is involved in regulating the neuronal size of mDA neurons and provided mechanistic insights into the development and maintenance of mDA neurons.

Keywords: mDA neurons; orphan nuclear receptor; protein tyrosine phosphatase receptor U; reduced neuronal size; tyrosine hydroxylase.