Peripheral Sensory Neurons Survive in the Absence of α- and γ-Synucleins

Abstract

Physiological functions of alpha-synuclein, a protein implicated in certain types of neurodegeneration, and two other members of the same family, beta-synuclein and gamma-synuclein, are not clearly understood. It has been suggested that synucleins are involved in intracellular processes associated with survival of neurons and their response to stress, and that changes of synuclein ratio might have deteriorating effects on neurons. In wild-type mice, sensory neurons of the peripheral nervous system express alpha-synuclein and notably high levels of gamma-synuclein, but targeted inactivation of either of these genes has no effect on these neurons. Here we produced double, alpha-synuclein/gamma-synuclein null mutant mice, which develop normally, are fertile, and show no obvious signs of pathology in adulthood. Survival of alpha/gamma-synuclein-deficient peripheral sensory neurons in vivo and in primary tissue culture is indistinguishable from survival of wild-type neurons. The absence of two synucleins does not lead to expression in sensory neurons of the third member of the family, beta-synuclein. Therefore, our results demonstrate that neurons with normally high levels of synuclein(s) can develop and survive normally in the absence of any of these proteins. This suggests that other intraneuronal mechanisms and pathways effectively compensate the loss of synuclein function in null mutant animals.