The authors use gene targeting in mouse embryonic stem cells where most of the β1-AR coding region is replaced with a neomycin cassette. From this step come the knockout mice, shown by Southern blot and Western blot that the gene change is properly made and the β1-protien is no longer present. The study then looked at the heart, where its signals and rhythm are checked by 125I-CYP binding, adenylate cyclase assays, catheter recordings, and isolated heart tests with isoproterenol, so the heart’s response to the loss of β1-AR is seen more clearly.