C57BL/6J mouse apolipoprotein A2 gene is deterministic for apnea

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

Does This Patient Have Acute Mountain Sickness?

“…[9][10][11][12][13][14][15] Although not yet demonstrated in humans, animal studies suggest that individual susceptibility to AMS can be explained by genetic differences in the respiratory drive. [16][17][18] The risk for AMS is as much as 2.06-fold (95% CI, 1.15-3.72) lower for people older than 50 years. 12,14,[19][20][21][22] Women may be more likely affected than men, 19,22,23 but this finding is not consistent.…”

“…Estimates of this risk vary by the type of diagnostic instrument used to establish a diagnosis of AMS . Although not yet demonstrated in humans, animal studies suggest that individual susceptibility to AMS can be explained by genetic differences in the respiratory drive . The risk for AMS is as much as 2.06-fold (95% CI, 1.15-3.72) lower for people older than 50 years .…”

Intranasal Leptin Prevents Opioid-induced Sleep-disordered Breathing in Obese Mice

“…However, our previous study (16) and current report demonstrate that obese C57BL/6J mice had a stable breathing pattern with infrequent apneas during sleep at baseline, which was significantly impaired by opioids. Sex (11), strain (49,50), and obesity status can modify respiratory responses to leptin and opioids.…”

Sleep Disorders and Genes

“…Moreover, CRISPR-Cas9-might be also considered to editing genes in sleep disorders, such as insomnia, OSA, narcolepsy, advanced sleep phase syndrome, or restless legs syndrome (100, 101; Figure 2). Indeed, it is needed to explore of the use of CRISPR-Cas9 in animal models of sleep disorders before to consider it a "bench-to-bedside" approach (102,103).…”