Phox2b mutation mediated by Atoh1 expression impaired respiratory rhythm and ventilatory responses to hypoxia and hypercapnia
- Department of Pharmacology, Instituto de Ciencias Biomedicas, Universidade de Sao Paulo, Brazil
- Department of Physiology and Biophysics, Instituto de Ciencias Biomedicas, University of Sao Paulo, Brazil
- Department of Pathology, College of Medicine, Ohio State University, United States
Figures
Figure 1
Functional respiratory changes observed in the Phox2b∆8 mutation in Atoh1cre-expressing cells.
Changes in (A) respiratory frequency (fR; breaths/min), (B) tidal volume (VT; μL/g), (C) minute ventilation (VE; μL/min/g), (D) inspiratory time (TI; s), (E) expiratory time (TE; s), (F) total cycle …
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Figure 1—source data 1
Raw respiratory parameters of control and Phox2bdelta8/Atoh1-cre mice.
- https://cdn.elifesciences.org/articles/73130/elife-73130-fig1-data1-v2.xlsx
Figure 2
Breath variability increased in adult mice.
Typical examples of Poincare plot graphs showing SD1 and SD2 from breath duration (TTOT) vs. duration of the subsequent breath (TTOT n+1) in (A) control and (B) mutant mice (Phox2b∆8, Atoh1cre) in …
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Figure 2—source data 1
Raw breath variability of control and Phox2bdelta8/Atoh1-cre mice.
- https://cdn.elifesciences.org/articles/73130/elife-73130-fig2-data1-v2.xlsx
Figure 3
Phox2bΔ8 in Atoh1cre cells impaired ventilatory responses to hypoxia and hypercapnia in neonates.
(A) Representative plethysmograph breathing traces in a control (top traces) and mutant (Phox2b∆8, Atoh1cre; bottom traces) neonate (P3) mice while ventilated with room air (normoxia; FiO2=0.21); …
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Figure 3—source data 1
Raw respiratory parameters of control and Phox2bdelta8/Atoh1-cre neonate mice under hypoxia and hypercapnia.
- https://cdn.elifesciences.org/articles/73130/elife-73130-fig3-data1-v2.xlsx
Figure 4
Phox2bΔ8 in Atoh1cre cells impaired ventilatory responses to hypoxia in adult.
(A) Representative plethysmograph breathing traces in a control and mutant (Phox2b∆8, Atoh1cre) adult (P45) mice while ventilated with room air (normoxia; FiO2=0.21); hypoxia (FiO2=0.08); and …
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Figure 4—source data 1
Raw respiratory parameters of control and Phox2bdelta8/Atoh1-cre adult mice under hypoxia and hypercapnia.
- https://cdn.elifesciences.org/articles/73130/elife-73130-fig4-data1-v2.xlsx
Figure 5
Adult mutant mice reduced Phox2b expression in the parafacial/retrotrapezoid nucleus (RTN) region.
Photomicrographs of ventrolateral medulla from (A) control and (C) mutant (Phox2b∆8, Atoh1cre) adult mice. Schematic drawings represent examples of coronal sections of ventrolateral medulla in (B) …
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Figure 5—source data 1
Raw numbers of neuronal profiles (Phox2b and TH) of control and Phox2bdelta8/Atoh1-cre adult mice.
- https://cdn.elifesciences.org/articles/73130/elife-73130-fig5-data1-v2.xlsx
Figure 6
Fos-activated neurons in the parafacial/retrotrapezoid nucleus (RTN) region in response to hypercapnia are reduced in mutant mice.
Photomicrographs of ventrolateral medulla from (A) control and (C) mutant (Phox2b∆8, Atoh1cre) mice exposed to hypercapnia (FiCO2=0.07). Schematic drawings represent coronal sections of …
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Figure 6—source data 1
Raw numbers of neuronal profiles (fos and TH) of control and Phox2bdelta8/Atoh1-cre adult mice under hypercapnia.
- https://cdn.elifesciences.org/articles/73130/elife-73130-fig6-data1-v2.xlsx
Figure 7
Schematic view of the mouse hindbrain control of breathing and the role of transcriptions factors and neuromodulators.
The respiratory parafacial region (pF) contains neurons involved in breathing regulation. Within the ventral aspect of the pF, retrotrapezoid nucleus (RTN) could be defined as a cluster of neurons …
Tables
Table 1
Genotyping primers.
| Mouse line | Strain name | Strain # | Obtained from | Primers | Band sizes |
|---|---|---|---|---|---|
| Atoh1Cre | B6.Cg-Tg(Atoh1-cre)1Bfri/J | Jax: 011104 | Jackson Laboratories | Tg FWD 5'-CCG GCA GAG TTT ACA GAA GC-3' | Tg = 450 bp |
| Tg REV 5'-ATG TTT AGC TGG CCC AAA TG-3' | CTR = 324 bp | ||||
| CTR FWD 5'-CTA GGC CAC AGA ATT GAA AGA TCT-3' | |||||
| CTR REV 5'-GTA GGT GGA AAT TCT AGC ATC ATC C-3' | |||||
| Phox2bΔ8 | B6.129(Cg)-Phox2btm1Rth/J | Jax: 025436 | David Rowitch, UCSF | FWD 5'-GCC CAC AGT GCC TCT TAA CTC-3' | Mutant = 450 bp |
| REV 5'-CGT ACT CTT AAA CGG GCG TCT C-3' | Wild type = 334 bp |
