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C57BL/6J mouse apolipoprotein A2 gene is deterministic for apnea
Carl B Gillombardo1, Rebecca Darrah2, Thomas E Dick3
1Department of Medicine, Cleveland Clinic Foundation, Cleveland, OH, United States.
Respiratory Physiology & Neurobiology
|November 7, 2016
Summary
Apolipoprotein AII (Apoa2) gene variants influence breathing control and apnea. This research identifies a novel pathway linked to adult sleep apnea risk.
Area of Science:
- Neuroscience
- Genetics
- Sleep Medicine
Background:
- Brainstem apolipoprotein AII (apoa2) mRNA expression is linked to breathing abnormalities in a mouse model of sleep apnea.
- The C57Bl/6J (B6) strain exhibits a correlation between apoa2 expression and apnea.
Purpose of the Study:
- To investigate the role of the apoa2 gene in breathing control and apnea.
- To determine if the B6 apoa2 gene variant contributes to the trait of apnea.
Main Methods:
- Plethysmography was used for in vivo measurements of breathing in apoa2 knockout (KO) mice, heterozygotes, and wild-type (WT) mice.
- An in situ brainstem-spinal cord preparation was utilized to compare KO and WT mice.
- B6xDBA recombinant inbred strains (RISs) were analyzed for apnea incidence.
Main Results:
- Apoa2 KO and heterozygote mice did not exhibit apnea during post-hypoxic breathing, unlike WT mice.
- In situ preparations showed reduced pauses and instability in phrenic bursting in KO compared to WT.
- RIS analysis revealed a higher number of apneas in strains with the B6 apoa2 allele.
Conclusions:
- The B6 apoa2 polymorphism directly impacts breath production.
- This finding suggests a novel genetic pathway influencing the risk of adult sleep apnea.
