Differences in Sleep-induced Hypoxia between A/J and DBA/2J Mouse Strains

Arnon E. Rubin, Vsevolod Y. Polotsky, Alexander Balbir, Jerry A. Krishnan, Alan R. Schwartz, Philip L. Smith, Robert S. Fitzgerald, Clarke G. Tankersley, Machiko Shirahata, Christopher P. O'Donnell

Research output: Contribution to journalArticlepeer-review

33 Scopus citations


In obstructive sleep apnea, hypoxic ventilatory sensitivity may affect the degree of hypoxic stress and sleep disruption that occurs in response to upper airway obstruction. We induced (1) sleep-induced hypoxia (SIH) or (2) sleep fragmentation (SF) without hypoxia for 5 days (12-hour light/dark cycle) in two inbred mouse strains with low (A/J) and high (DBA/2J) hypoxic ventilatory sensitivities. During SIH, the time to arousal (26.4 ± 1.1 vs. 21.3 ± 1.5 seconds, p < 0.025) and the severity of hypoxic exposure (nadir Fl02: 11.5 ± 0.4 vs. 13.6 ± 0.1%, p < 0.002) was greater in A/J than DBA/2J mice. Furthermore, A/J mice had a greater frequency of hypoxic events (640 ± 29 vs. 368 ± 33 events per 24 hours, p < 0.001) and total sleep time (47.5 ± 2.8% vs. 26.5 ± 2.4% per 24 hours, p < 0.0001) during SIH than DBA/2J mice. In contrast, the event characteristics and total sleep time during SF were the same in both strains. Furthermore, in the light phase, both strains showed a longer (p < 0.01) time to arousal during SIH and SF compared with the dark phase. We conclude that genetic background can influence respiratory events and sleep architecture during SIH and that the arousal threshold is subject to circadian variation. Our data imply that individuals with low hypoxic sensitivity may be at a greater risk for hypoxia-related complications of obstructive sleep apnea.

Original languageEnglish (US)
Pages (from-to)1520-1527
Number of pages8
JournalAmerican journal of respiratory and critical care medicine
Issue number12
StatePublished - Dec 15 2003
Externally publishedYes


  • Carotid body
  • Genetics
  • Hypoxic ventilatory response
  • Obstructive sleep apnea
  • Sleep fragmentation

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine


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