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Spontaneous peripheral oxygen desaturation and apnea events in mice vary by strain and inspired oxygen level
Preprint   Open access

Spontaneous peripheral oxygen desaturation and apnea events in mice vary by strain and inspired oxygen level

Hardik Kalra, Anastasiia Vasileva, Charles R Jedlicka, Mikhail Vasilyev, Michelle A Buckman, Zishan Zhang, Brian K Gehlbach, Junjie Liu, Lara R DeRuisseau, Mark W Chapleau, …
bioRxiv
09/05/2025
DOI: 10.1101/2025.09.01.673515
PMCID: PMC12424765
PMID: 40950039
url
https://doi.org/10.1101/2025.09.01.673515View
Preprint (Author's original)This preprint has not been evaluated by subject experts through peer review. Preprints may undergo extensive changes and/or become peer-reviewed journal articles. Open Access

Abstract

Mouse models of chronic intermittent hypoxia are widely used in research to understand the role of sleep apnea in disease pathogenesis. Mice exposed to periodic reductions in F I O 2 model arterial desaturations observed in humans and recapitulate many comorbidities of sleep apnea. Here, we perform a detailed characterization and confirm reports that mice in room air experience spontaneous, periodic desaturation events. We measured peripheral oxygen saturation in the four mouse strains most commonly used in intermittent hypoxia research (C57BL/6J, CD1, BALB/c, and 129S1) and subjected them to conscious barometric plethysmography to measure oxygen desaturations and apneas simultaneously and took measurements across a range of fractional inspired oxygen (F I O 2 ). As expected, all strains experienced periodic apneas that were followed by desaturations and decreasing F I O 2 resulted in a reduction of spontaneous apneic events (p = 0.001). Surprisingly, most oxygen desaturations were not preceded by apneas or hypopneas, and mice experienced more desaturations at lower F I O 2 (p < 0.001), despite less frequent apneas. Furthermore, we found strain differences in ventilatory response consistent with prior findings and a novel strain difference in 129S1 mice. These data suggest that spontaneous desaturations are caused not only by apneas and hypopneas but also by other mechanisms, independent of respiration. Our findings provide important context for mouse models of sleep apnea and associated diseases, and future work should explore the extent to which these findings are relevant in humans.Mouse models of chronic intermittent hypoxia are widely used in research to understand the role of sleep apnea in disease pathogenesis. Mice exposed to periodic reductions in F I O 2 model arterial desaturations observed in humans and recapitulate many comorbidities of sleep apnea. Here, we perform a detailed characterization and confirm reports that mice in room air experience spontaneous, periodic desaturation events. We measured peripheral oxygen saturation in the four mouse strains most commonly used in intermittent hypoxia research (C57BL/6J, CD1, BALB/c, and 129S1) and subjected them to conscious barometric plethysmography to measure oxygen desaturations and apneas simultaneously and took measurements across a range of fractional inspired oxygen (F I O 2 ). As expected, all strains experienced periodic apneas that were followed by desaturations and decreasing F I O 2 resulted in a reduction of spontaneous apneic events (p = 0.001). Surprisingly, most oxygen desaturations were not preceded by apneas or hypopneas, and mice experienced more desaturations at lower F I O 2 (p < 0.001), despite less frequent apneas. Furthermore, we found strain differences in ventilatory response consistent with prior findings and a novel strain difference in 129S1 mice. These data suggest that spontaneous desaturations are caused not only by apneas and hypopneas but also by other mechanisms, independent of respiration. Our findings provide important context for mouse models of sleep apnea and associated diseases, and future work should explore the extent to which these findings are relevant in humans.

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