| First Author | Buettner JM | Year | 2021 |
| Journal | iScience | Volume | 24 |
| Issue | 11 | Pages | 103376 |
| PubMed ID | 34825141 | Mgi Jnum | J:348130 |
| Mgi Id | MGI:6833980 | Doi | 10.1016/j.isci.2021.103376 |
| Citation | Buettner JM, et al. (2021) Central synaptopathy is the most conserved feature of motor circuit pathology across spinal muscular atrophy mouse models. iScience 24(11):103376 |
| abstractText | Spinal muscular atrophy (SMA) is a neurodegenerative disease caused by reduced survival motor neuron (SMN) protein. Recently, SMN dysfunction has been linked to individual aspects of motor circuit pathology in a severe SMA mouse model. To determine whether these disease mechanisms are conserved, we directly compared the motor circuit pathology of three SMA mouse models. The severe SMNDelta7 model exhibits vast motor circuit defects, including degeneration of motor neurons, spinal excitatory synapses, and neuromuscular junctions (NMJs). In contrast, the Taiwanese model shows very mild motor neuron pathology, but early central synaptic loss. In the intermediate Smn (2B/-) model, strong pathology of central excitatory synapses and NMJs precedes the late onset of p53-dependent motor neuron death. These pathological events correlate with SMN-dependent splicing dysregulation of specific mRNAs. Our study provides a knowledge base for properly tailoring future studies and identifies central excitatory synaptopathy as a key feature of motor circuit pathology in SMA. |
