Hereditary sensory and autonomic neuropathies (HSANs) are a group of recessive genetic disorders affecting the sensory and autonomic components of the peripheral nervous system (PNS). Compared with somatosensory dysfunctions, the pathogenesis of visceral dysfunction in HSANs remains understudied. This study investigated the neural circuit mechanisms underlying the arrhythmias observed in conditional Dystonin ( Dst ) gene-trap mice, an animal model of HSAN type VI (HSAN-VI) in which Cre recombinase inactivates Dst expression in selective neural circuits. Inactivation of the Dst gene in PNS neurons using Advillin-Cre caused the degeneration of sensory and sympathetic ganglionic neurons. This was accompanied by arrhythmia, characterized by increased heart rate variability and irregular pulse frequency, which was prominent under isoflurane anesthesia and occurred in the absence of protein aggregate cardiomyopathy. Furthermore, selective inactivation of the Dst gene in PNS sensory neurons using Vglut2-Cre resulted in similar dysregulation of cardiac rhythm. These findings suggest that arrhythmias caused by Dst mutations arise from the disruption of visceral afferent circuits, and that these neural circuits could be potential therapeutic targets for visceral dysfunction in HSAN-VI.
Yoshioka et al. (Wed,) studied this question.