Modulation of dopaminergic receptor activity does not rescue Grk4 LOF kidney phenotypes. (A) Antagonism of dopaminergic receptor by SCH39166 failed to shorten the nhe3a expression domain. n=3 experiments with 54-67 embryos in total. ns; P>0.9999 data were analyzed using the Kruskal-Wallis test with Dunn's multiple comparison post-test). (B) The dopamine receptor antagonist, SCH39166, did not reduce the percentage of Grk4 LOF embryos developing glomerular cysts. n=4 experiments with 134-155 embryos in total. ****P<0.0001 ns, P=0.6176 (data were analyzed using a two-sided Fisher's exact test with the Bonferroni correction applied). (C) Nhe3a expression in embryos treated with the vehicle (CTRL) or dopamine. Scale bar, 200 μm. (D) Dopamine administration did not alter the length of the nhe3a expression domain in Grk4-depleted embryos. n=3 experiments with 64-72 embryos in total. ns, P=0.3242 (data were analyzed using a two-tailed Welch's test). (E) Fenoldopam treatment did not induce cyst formation. n=4 experiments with 94-96 embryos in total. (F) Stimulation of dopaminergic receptor using fenoldopam did not result in hydrocephalus formation. n=6 experiments with 134-135 embryos in total. ns, not significant; DA, dopamine; Grk4, G protein-coupled receptor kinase 4; LOF, loss-of-function; Nhe3, sodium-hydrogen exchanger 3; Grk4, G protein-coupled receptor kinase 4; CTRL, control; MO, morpholino oligonucleotide; fenold., fenoldopam.
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