SMΝΔ7 mice show breathing and airflow defects with significant pathology of respiratory and oral tract tissues.

INTRODUCTION

Spinal muscular atrophy (SMA) is a neurodegenerative disorder caused by SMN1 mutations, leading to SMN protein deficiency and motor neuron loss. While progressive weakness, respiratory defects, and oral dysfunction are well-documented in patients, the underlying pathophysiology of breathing and bulbar deficits remains understudied in SMA animal models.

METHODS

We evaluated breathing and oral function in the SMN∆7 mouse model of severe SMA. Respiratory parameters and chemoreflexes were assessed via whole-body plethysmography. To identify underlying structural changes, we performed histological analysis on lung tissue, the phrenic and hypoglossal nerves, and the muscles driving respiration and oral function.

RESULTS

SMN∆7 mice exhibited baseline respiratory alterations and chemoreflex deficits. Histological analysis revealed reduced neuromuscular junction (NMJ) occupancy in respiratory and oral muscles, alongside axonal pathology in the phrenic and hypoglossal nerves and structural degradation in lung tissue.

DISCUSSION: These data provide the first physiological and histological evidence of linked respiratory and oral dysfunction in the SMN∆7 mouse. Because these deficits closely approximate the clinical presentation seen in SMA patients, this model represents a valuable tool for testing therapies targeted at bulbar and respiratory failure.