RNAseq of motor neurons and neurons with differential vulnerability isolated from a mouse model of spinal muscular atrophy using laser capture microdissection

Motor neurons are selectively vulnerable in spinal muscular atrophy (SMA). However, some brainstem motor neuron groups, including oculomotor and trochlear, which innervate the muscles around the eyes, are for unknown reasons spared. Here, we investigate the transcriptional dynamics in discrete neuronal populations in health and SMA to identify mechanisms of vulnerability and resistance. Such mechanisms could reveal targets for future gene therapy studies aimed towards preserving vulnerable motor neurons. We used laser capture microdissection to isolate discrete neurons from the ‘delta7’ mouse model of SMA (Smn-/-/SMN2+/+/SMN∆7+/+) and littermate controls (Smn+/+/SMN2+/+/SMN∆7+/+) (Jax Stock No 005025). We analyzed a total of 168 samples with 3-7 biological replicates per condition. We included 6 neuronal groups with differential vulnerability in this disease and investigated 3 time points throughout disease progression including a pre-, early and late symptomatic stage (postnatal days 2, 5 and 10).