Related Experiment Video
Updated: Mar 13, 2026
Quantification of Atherosclerosis in Mice
Published on: June 12, 2019
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.
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.
Insights
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.
