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Choosing the optimal mouse model for the study of late-onset spinal muscular atrophy: Why the 4-copy SMN2 model offers ideal translational relevance

Title: Choosing the optimal mouse model for the study of late-onset spinal muscular atrophy: Why the 4-copy SMN2 model offers ideal translational relevance
Authors: Leo, Markus; Schmitt, Linda-Isabell; Liebig, Kai Christine; Hezel, Stefanie; Neuhoff, Svenja; Roos, Andreas; Kleinschnitz, Christoph; Weiler, Markus; Günther, Rene; Schara-Schmidt, Ulrike; Claus, Peter; Hagenacker, Tim
Source: Journal of Neuromuscular Diseases ; ISSN 2214-3599 2214-3602
Publisher Information: SAGE Publications
Publication Year: 2026
Description: Spinal muscular atrophy (SMA) comprises a spectrum of clinical severities, yet the pathomechanisms of late-onset forms (Type III) remain insufficiently understood. While severe early-onset SMA has been extensively investigated using existing models, their translational relevance to adult disease is limited. Here, we recommend the 4-copy SMN2 mouse (FVB.Cg- Smn1 tm1Hung Tg( SMN2 )2Hung/J) as the most appropriate model for late-onset SMA. This model exhibits delayed onset, progressive motor dysfunction, and extended survival, enabling the study of chronic neurodegenerative processes, including astrocyte-mediated motor neuron pathology. Its prolonged therapeutic window makes the model suitable for mechanistic and translational investigations of late-onset SMA.
Document Type: article in journal/newspaper
Language: English
DOI: 10.1177/22143602251405151
Availability: https://doi.org/10.1177/22143602251405151; https://journals.sagepub.com/doi/pdf/10.1177/22143602251405151; https://journals.sagepub.com/doi/full-xml/10.1177/22143602251405151
Rights: https://creativecommons.org/licenses/by-nc/4.0/ ; https://journals.sagepub.com/page/policies/text-and-data-mining-license
Accession Number: edsbas.B327B6AB
Database: BASE