Strategy for generation of the GRK1-S21A mutant mouse. A, Genomic clone of wild-type Grk1. Green arrows represent areas covered by the vector homology arms (long arrow is the 5′ arm, short arrow is the 3′ arm). Orange arrows indicate the positions of exons 1 and 7, respectively. The other exons are represented by blue bars. B, Generation of the mutant S21A-GRK1 allele. The wild-type locus is shown on top. An expanded view of the first two exons is shown in the middle containing the Ser21Ala (S21A) mutation and a PKG-neo cassette with loxP sites on either end. The lower panel shows the entire targeted allele with the S21A mutation, the PKG-neo cassette and the 7 exons