LAMA2-related muscular dystrophy alters Schwann cell calcium homeostasis and increases peripheral nerve inflammation

Wang, J.; Khati, M.; Heron, M.; Munir, A.; Akinyele, O.; Johnson, M. A.; Vockley, J.; Pandey, U. B.; Kemaladewi, D. U.

doi:10.64898/2026.10.27.762325

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bioRxiv · 10.64898/2026.10.27.762325

LAMA2-related muscular dystrophy alters Schwann cell calcium homeostasis and increases peripheral nerve inflammation

Wang, J.·Khati, M.·Heron, M.·Munir, A.·Akinyele, O.·Johnson, M. A.·Vockley, J.·Pandey, U. B.·Kemaladewi, D. U.

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Abstract

LAMA2-related muscular dystrophy (LAMA2-RD) affects skeletal muscle and peripheral nerves, yet the consequences of LAMA2 deficiency on peripheral nerve integrity beyond early postnatal development remain incompletely understood. We investigated sciatic nerve architecture and molecular alterations across postnatal life in hypomorphic Lama2dy2J/dy2J mice. LAMA2 localizes around the abaxonal surface of myelinating Schwann cells in control nerves. LAMA2-deficient nerves exhibited patchy regions lacking myelinated axons from early postnatal stages into adulthood, including expanded Remak bundles along with axons completely lacking normal Schwann cell ensheathment. In adult nerves, myelin infolding and reduced myelin circularity revealed abnormalities in the architecture of myelin that had formed. Bulk sciatic nerve RNA sequencing identified altered calcium-signaling and immune-related transcriptional signatures. Complementary Fura Red measurements in primary nerve-derived Schwann cell cultures demonstrated decreased intracellular calcium in LAMA2-deficient samples, while ATP-evoked responses were preserved. Older LAMA2-deficient nerves also exhibited increased CD45+CD11b+ myeloid-cell infiltration. Together, these observations extend the characterization of LAMA2-associated neuropathy into adulthood and identify calcium homeostasis and neuroimmune responses as candidate processes relevant to persistent peripheral nerve pathology.

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Wang, J., Khati, M., Heron, M., Munir, A., Akinyele, O., Johnson, M. A., Vockley, J., Pandey, U. B., Kemaladewi, D. U.. 2026-11-02. LAMA2-related muscular dystrophy alters Schwann cell calcium homeostasis and increases peripheral nerve inflammation. https://doi.org/10.64898/2026.10.27.762325

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