However, in mice with a non-functional G protein-receptor kinase 2, which prevents recruitment of ß-arrestin by MORs, the dose of fentanyl needed to reduce breathing rate was signiflcantly lower than wild-type mice (Kliewer et al., 2019), suggesting that ß-arrestin does not mediate respiratory depression by opioid drugs. This evidence concerns the gene SAG and Respiratory insufficiency due to muscle weakness.