A MusD Retrotransposon Insertion in the Mouse Slc6a5 Gene Causes Alterations in Neuromuscular Junction Maturation and Behavioral Phenotypes

摘要: Glycine is the major inhibitory neurotransmitter in spinal cord and some brain regions. The presynaptic glycine transporter, GlyT2, required for sustained glycinergic transmission through reuptake recycling of glycine. Mutations SLC6A5, encoding cause hereditary hyperekplexia humans, similar phenotypes knock-out mice, variants are associated with schizophrenia. We identified a spontaneous mutation mouse Slc6a5, caused by MusD retrotransposon insertion. GlyT2 protein undetectable homozygous mutants, indicating null allele. Homozygous mutant mice normal at birth, but develop handling-induced spasms five days age, only survive two weeks, allow study early activity-regulated developmental processes. At neuromuscular junction, synapse elimination switch from embryonic to adult acetylcholine receptor subunits hastened, consistent presumed increase motor neuron activity, transcription receptors elevated. Heterozygous which show no reduction lifespan nonetheless have reduced levels thermal sensitivity hot-plate test, differences repetitive grooming decreased sleep time home-cage monitoring. Open-field elevated plus-maze tests did not detect anxiety-like behaviors; however, latter showed hyperactivity phenotype. Importantly, observed schizophrenia models. Thus, mutations Slc6a5 changes junction development as homozygotes, behavioral heterozygotes, their usefulness studies related dysfunction.