Zebrafish model of SNUPN loss-of-function recapitulates limb-girdle muscular dystrophy features

Loss-of-function variants in SNUPN, the gene encoding the nuclear import factor Snurportin-1 (SPN1), were recently identified as the cause of a novel subtype of limb-girdle muscular dystrophy (LGMD). SPN1 is required for the nuclear import of spliceosomal small nuclear ribonucleoproteins (snRNPs), making it essential for pre-mRNA splicing and, by extension, normal gene expression across tissues. Despite the clinical description, the mechanistic basis of muscle pathology in SNUPN-related LGMD has been poorly understood.

A preprint posted to bioRxiv on 29 September 2026 describes a zebrafish snupn loss-of-function model generated by the authors to address this gap. Mutant larvae developed severe locomotor impairment by six days post-fertilisation, with histological and molecular analyses revealing disruption of muscle niche integrity and depletion of myogenic progenitor cells — the satellite-cell-like population responsible for muscle maintenance and repair. The authors report that SPN1 deficiency compromises the capacity for muscle regeneration, suggesting that the progressive nature of LGMD in affected individuals may in part reflect an inability to replenish damaged fibres.

The zebrafish model recapitulates key pathological features observed in patient muscle biopsies and provides a platform for future therapeutic screening. This work is a preprint and has not yet been peer reviewed (bioRxiv doi: 10.64898/2026.09.24.749599).