Smn deficiency causes neuritogenesis and neurogenesis defects in the retinal neurons of a mouse model of spinal muscular atrophy

摘要: The eye is an excellent model for the study of neuronal development and pathogenesis central nervous system disorders because its relative ease accessibility well-characterized cellular makeup. We have used this to spinal muscular atrophy (SMA), autosomal recessive neuromuscular disease caused by deletions or mutations in survival motor neuron 1 gene (SMN1). investigated expression pattern mouse Smn mRNA protein neural retina optic nerve wild type mice. present retinal ganglion cells amacrine within as well glial nerve. Histopathological analysis phenotype stage SMA mice revealed that deficiency associated with a reduction cell axon number nerve, compromised processes altered organization neurofilaments retina. Whole mount preparation primary culture provided further evidence abnormal synaptogenesis neurofilament accumulation neurites Smn-deficient neurons. A subset absent, cell-autonomous fashion, Finally, retinas electroretinograms. Altogether, our has demonstrated defects axodendritic outgrowth composition Smn-depleted neurons, indicating role neuritogenesis neurogenesis, providing us insight into SMA. © 2010 Wiley Periodicals, Inc. Develop Neurobiol 71: 153-169, 2011