A mouse strain lacking functional GRK4 gene

GRK4 is prominently expressed in testes, with expression also in select brain regions (cerebellum) and other organs and cell types. GRK4 has been implicated in regulation of cerebellar mGluRl and GABA, receptors, and may be important in motor coordination. Human polymorphisms in GRK4 are associated with hypertension, and primary kidney tubule cells expressing GRK4 variants exhibit dysregulation of dopamine Dl receptors. GRK4 may be an important regulator controlling blood pressure. Unexpected expression of GRK4 in tumor-infiltrating neutrophils in human lung adenocarcinomas suggests that GRK4 is a marker for tumor regression/control and that GRK4 function may be important to beneficial responses of innate immune cells in targeting tumors.

Deletion of the GRK4 gene in mice has been accomplished using gene targeting in embryonic stem cells followed by injection of targeted ES cells into mouse embryo blastocysts. Loss of the both alleles of the GRK4 gene does not affect viability of mice. Because GRK4 expression is so prominent in testis, mice lacking GRK4 were tested for fertility. Male GRK4 homozygote mice are fertile, and have litters of normal size. Sperm isolated from male GRK4 homozygote mice display normal swimming and capacitation responses in vitro.