Carl B Gillombardo1, Rebecca Darrah2, Thomas E Dick3, Michael Moore4, Nathan Kong5, Michael J Decker6, Fang Han7, Motoo Yamauchi8, Mathias Dutschmann9, Sausan Azzam10, Kingman P Strohl11. 1. Department of Medicine, Cleveland Clinic Foundation, Cleveland, OH, United States. 2. Department of Genetics and Genome Science, Case Western Reserve University, Cleveland, OH, United States. 3. Department of Medicine, University Hospitals Case Medical Center, Cleveland, OH, United States; School of Medicine, Case Western Reserve University, Cleveland, OH, United States. 4. Department of Medicine, University Hospitals Case Medical Center, Cleveland, OH, United States. 5. Feinberg School of Medicine, Northwestern University, Chicago, IL, United States. 6. Francis Payne Bolton School of Nursing, Case Western Reserve University, Cleveland, OH, United States. 7. People's Hospital, Beijing Medical University, Beijing, China. 8. Nara Medical University, Nara, Japan. 9. Florey Institute of Neuroscience and Mental Health, University of Melbourne, Australia. 10. Department of Nutrition, Case School of Medicine, Cleveland, OH, United States. 11. Department of Medicine, University Hospitals Case Medical Center, Cleveland, OH, United States; School of Medicine, Case Western Reserve University, Cleveland, OH, United States. Electronic address: kingman.strohl@va.gov.
Abstract
RATIONALE: Brainstem apolipoprotein AII (apoa2) mRNA expression correlates with apnea in breathing present in the adult C57Bl/6J (B6) sleep apnea model. OBJECTIVES: To test the hypothesis that the B6 apoa2 gene contributes to the trait, we performed plethysmographic testing in apoa2 knock out (KO: -/-) mice, an in situ brainstem-spinal cord preparation comparing KO to WT (+/+) mice, and B6xDBA recombinant inbred strains (RISs). MEASUREMENTS AND MAIN RESULTS: Apoa2 WT do, but KO and heterozygote (+/-) mice do not exhibit apnea during post-hypoxic breathing, measured in vivo. In the in situ model, pauses and instability in fictive phrenic bursting are substantially reduced in KO vs. WT preparations. In 24 RISs, apnea number in vivo was higher in strains with B6 apoa2 than with DBA apoa2 alleles. CONCLUSIONS: The B6 apoa2 polymorphism is directly involved in breath production, and its identification suggests a novel pathway influencing risk for adult sleep apnea. Published by Elsevier B.V.
RATIONALE: Brainstem apolipoprotein AII (apoa2) mRNA expression correlates with apnea in breathing present in the adult C57Bl/6J (B6) sleep apnea model. OBJECTIVES: To test the hypothesis that the B6 apoa2 gene contributes to the trait, we performed plethysmographic testing in apoa2 knock out (KO: -/-) mice, an in situ brainstem-spinal cord preparation comparing KO to WT (+/+) mice, and B6xDBA recombinant inbred strains (RISs). MEASUREMENTS AND MAIN RESULTS:Apoa2 WT do, but KO and heterozygote (+/-) mice do not exhibit apnea during post-hypoxic breathing, measured in vivo. In the in situ model, pauses and instability in fictive phrenic bursting are substantially reduced in KO vs. WT preparations. In 24 RISs, apnea number in vivo was higher in strains with B6 apoa2 than with DBAapoa2 alleles. CONCLUSIONS: The B6 apoa2 polymorphism is directly involved in breath production, and its identification suggests a novel pathway influencing risk for adult sleep apnea. Published by Elsevier B.V.
Authors: C Barton Gillombardo; Motoo Yamauchi; Mark D Adams; Jesse Dostal; Sam Chai; Michael W Moore; Lucas M Donovan; Fang Han; Kingman P Strohl Journal: J Appl Physiol (1985) Date: 2012-04-26
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