Pompe disease is a
lysosomal storage disease resulting from absence or deficiency of
acid α-
glucosidase (GAA). Tongue-related disorders including
dysarthria,
dysphagia, and
obstructive sleep apnea are common in
Pompe disease. Our purpose was to determine if designer receptors exclusively activated by
designer drugs (DREADDs) could be used to stimulate tongue motor output in a mouse model of
Pompe disease. An adeno-associated virus serotype 9 (AAV9) encoding an excitatory DREADD (AAV9-hSyn-hM3D(Gq)-mCherry, 2.44 × 1010 vg) was administered to the posterior tongue of 5-7-wk-old Gaa null (Gaa-/-) mice. Lingual EMG responses to
intraperitoneal injection of saline or a DREADD
ligand (JHU37160-dihydrochloride, J60) were assessed 12 wk later during spontaneous breathing. Saline injection produced no consistent changes in lingual EMG. Following the DREADD
ligand, there were statistically significant (P < 0.05) increases in both tonic and phasic inspiratory EMG activity recorded from the posterior tongue. Brainstem histology confirmed mCherry expression in hypoglossal (XII) motoneurons in all mice, thus verifying retrograde movement of the AAV9 vector. Morphologically, Gaa-/- XII motoneurons showed histological characteristics that are typical of
Pompe disease, including an enlarged
soma and vacuolization. We conclude that lingual delivery of AAV9 can be used to drive functional expression of DREADD in XII motoneurons in a mouse model of
Pompe disease.NEW & NOTEWORTHY In a mouse model of
Pompe disease, lingual injection of adeno-associated virus (AAV) serotype 9 encoding DREADD was histologically verified to produce transgene expression in hypoglossal motoneurons. Subsequent intraperitoneal delivery of a DREADD
ligand stimulated tonic and phase tongue motor output.In a mouse model of
Pompe disease, lingual injection of adeno-associated virus (AAV) serotype 9 encoding DREADD was histologically verified to produce transgene expression in hypoglossal motoneurons. Subsequent intravenous delivery of a DREADD
ligand stimulated tonic and phase tongue motor output.