〔Abstract〕 Objective To generate a G protein-coupled receptor kinase 2(GRK2) heterozygous(GRK2+/-) mice by CRISPR/Cas9 for investigating the pathogenic role and therapeutic implication of GRK2.Methods GRK2 targeting vector was constructed and the mixture of single guide RNA and Case9 mRNA was microinjected into zygotes of female C57 BL/6 mouse to generate gene mutation in Exon3. We got both 13 bp-deletion and 19 bp-deletion GRK2+/-miceaccording to genotyping performed through PCR and gene sequencing. Since GRK2 homozygous are embryonic lethality,we cross-bred 19 bp-deletion F0 GRK2+/-mice with C57 BL/6 to obtain stable 19 bp-deletion F1 generation of GRK2+/-mice for propagation and the following experiments. Results The genotype of GRK2+/-mouse was steady with significant lower body weight compared with C57 BL/6 mouse at the same age. Western blot results showed that almost half of the GRK2 protein expression was reduced in immune organs like spleen and thymus as well as other tissues. Conclusion This GRK2 targeted genetically engineered mouse model will provide a promising approach for understanding the role of GRK2 in the development of diverse organs and cells as well as its pathogenic role and therapeutic implications in chronic diseases.