Neurons expressing the highest levels of gamma-synuclein are unaffected by targeted inactivation of the gene.
Homologous recombination in ES cells was employed to generate mice with targeted deletion of the first three exons of the gamma-synuclein gene. Complete inactivation of gene expression in null mutant mice was confirmed on the mRNA and protein levels. Null mutant mice are viable, are fertile, and do not display evident phenotypical abnormalities. The effects of gamma-synuclein deficiency on motor and peripheral sensory neurons were studied by various methods in vivo and in vitro. These two types of neurons were selected because they both express high levels of gamma-synuclein from the early stages of mouse embryonic development but later in the development they display different patterns of intracellular compartmentalization of the protein. We found no difference in the number of neurons between wild-type and null mutant animals in several brain stem motor nuclei, in lumbar dorsal root ganglia, and in the trigeminal ganglion. The survival of gamma-synuclein-deficient trigeminal neurons in various culture conditions was not different from that of wild-type neurons. There was no difference in the numbers of myelinated and nonmyelinated fibers in the saphenous nerves of these animals, and sensory reflex thresholds were also intact in gamma-synuclein null mutant mice. Nerve injury led to similar changes in sensory function in wild-type and mutant mice. Taken together, our data suggest that like alpha-synuclein, gamma-synuclein is dispensable for the development and function of the nervous system.
Pubmed ID: 14585981 RIS Download
Animals | Base Sequence | Cell Compartmentation | Cell Survival | Cells, Cultured | DNA | Embryonic and Fetal Development | Female | Gene Expression | Gene Targeting | Male | Mice | Mice, Inbred C57BL | Mice, Knockout | Motor Neurons | Nerve Tissue Proteins | Nervous System | Neurons | Neurons, Afferent | RNA, Messenger | Reflex | Synucleins | Trauma, Nervous System | alpha-Synuclein | gamma-Synuclein