Journal: Cell
Article Title: Divergent sensory pathways of sneezing and coughing
doi: 10.1016/j.cell.2024.08.009
Figure Lengend Snippet: (A) Genetic ablation of MrgprC11 + sensory neurons. Diagram showing the genetic strategy for specific ablation of MrgprC11 + sensory neurons. Representative images show that MrgprC11 + sensory neurons were ablated by diphtheria toxin (DTX) in the trigeminal ganglia from tamoxifen-treated Mrgprc11 CreERT2 ; Avil iDTR mice (called MrgprC11 DTR mice), but not from control Avil iDTR mice (indicated by arrows), as revealed by immunostaining for MrgprC11. (B) Genetic ablation of MrgprC11 + sensory neurons abolished the sneezing responses to MrgprC11 agonists NPFF (20 nmol in 2 μL/nostril) and BAM 8–22 (20 nmol in 2 μL/nostril) compared with control Avil iDTR mice. (C) Sneezing responses to aerosolized histamine solution (His, 100 mM), serotonin (5-HT, 1 mM), and capsaicin (Cap, 12 μM) were virtually abolished in MrgprC11 + neuron-ablated mice compared with control Avil iDTR mice. (D and E) In the mouse models of acute and chronic allergic rhinitis, sneezing responses to allergen (ovalbumin, 0.2 mg in 2 μL PBS/nostril) challenge was significantly reduced in MrgprC11 + neuron-ablated mice compared with control Avil iDTR mice. (F) Representative images of the whole-mount nasal mucosa from normal and allergic Mrgprc11 CreERT2 ; ROSA26 tdTomato/+ mice. Note the accumulation and degranulation of avidin-stained mast cells (green, indicated by arrows) in the allergic mice. The bar graph shows the proportion of mast cells closely associated with MrgprC11 + sensory fibers (red) in allergic mice ( n = 4 nasal mucosa explants). (G) Sneezing responses induced by aerosolized histamine solution (100 mM) were inhibited by nasal application of QX-314 (1%, 2 μL) with BAM (2 nmol), compared with the control groups pretreated with either BAM (2 nmol in 2 μL) or QX-314 (1%, 2 μL) alone. (H and I) In both acute and chronic allergic rhinitis models, allergen ovalbumin-induced sneezing responses were significantly suppressed by pretreatment of QX-314 (1%, 2 μL) with BAM (2 nmol) compared with the control groups pretreated with either BAM (2 nmol in 2 μL) or QX-314 (1%, 2 μL) alone. Each dot represents an individual mouse ( n = 6–11 mice/group). Data are presented as mean ± SEM. ** p ≤ 0.01; *** p ≤ 0.001; ns, not significant. All images shown are representative of at least three biological replicates. Scale bars, 50 μm. See also and .
Article Snippet: Three weeks after the completion of tamoxifen treatment, mice were given two intraperitoneal ( i.p. ) injections (three days apart) of 40 μg/kg of diphtheria toxin (DTX, List labs, 150) in saline.
Techniques: Control, Immunostaining, Avidin-Biotin Assay, Staining
