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bioRxiv · 10.64898/2026.07.27.740920

Age-dependent peripheral nerve and Schwann cell abnormalities in a mouse model of late-onset spinal muscular atrophy

Liebig, K. C.·Bense, N.·Schmitt, L.-I.·Hezel, S.·Kleinschnitz, C.·Leo, M.·Hagenacker, T.
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Abstract

Spinal muscular atrophy (SMA) is increasingly recognized as a multisystem disorder involving non-neuronal cells, yet the role of Schwann cells (SCs) in late-onset SMA (loSMA) remains unclear. We investigated age-dependent peripheral nerve pathology in a four-copy SMN2 mouse model of loSMA. Sciatic nerves from wild-type and loSMA mice were analyzed at postnatal (P) days 20, 35, 70, and >100 using semi-thin morphometry, immunofluorescence for MBP, Sox10, Sox2, and F4/80, and nerve conduction studies. loSMA nerves showed reduced myelin thickness at all time points and smaller axon diameters at P20 and P35. G- ratios were reduced at P20 but increased from P35 onward, indicating progressively altered axon-myelin relationships. MBP immunofluorescence intensity, compound muscle action potential amplitude, and nerve conduction velocity were reduced in loSMA mice at P>100. The proportion of Sox2+ SCs increased from P35 onward, while Sox10+ cell abundance increased at later stages. F4/80+ macrophages were transiently elevated at P35 and correlated with Sox2+ cell numbers at this stage. These findings demonstrate age-dependent myelin abnormalities, altered SC states, and transient accumulation of macrophages in loSMA peripheral nerves. Whether these changes are SC-autonomous or secondary to chronic axonal dysfunction remains to be determined.

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Liebig, K. C., Bense, N., Schmitt, L.-I., Hezel, S., Kleinschnitz, C., Leo, M., Hagenacker, T.. 2026-07-30. Age-dependent peripheral nerve and Schwann cell abnormalities in a mouse model of late-onset spinal muscular atrophy. https://doi.org/10.64898/2026.07.27.740920

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