Genetic Analysis Of The Biological Effect Of Excess Iodide In C.Elegans

Iodine is an essential trace element for the biosynthesis of thyroid hormones. Iodide deficiency is a major cause of hypothyroidism and mental retardation, while excess iodide intake is believed to be a risk factor for several thyroidal diseases. To date little is known about the molecular mechanism that underlies the biological effects of excess iodide intake. And the effects on animals other than mammals are less clear and little studies had been performed in C.elegans.Objective:To study the biological effect of excess iodide in C. elegans, realize the involved genes and undercover the molecular mechanism.Methods:Wild-type young adults were grown in NGM plate supplemented with NaI at different concentrations and their F1progeny were observed. Mutants were generated by EMS (ethyl methanesulfonate) mutagenesis and tested for growth and propagation in excess iodide, and then clone the related genes. ROS (reactive oxygen species) levels were measured using DCF-DA(2’,7’-Dichlorodihydrofluorescein diacetate).Results:Wild-type animals exhibit a reversible developmental arrest when excess iodide is supplied in the culture media. In our EMS forward genetic screen,10000F2s were checked for mutants that can survive in excess iodide and12mutations were isolated finally. Complementation test suggest that they affect at least four genes which might located on chromosome I and IV respectively. And to date, two of them were cloned, which encode the C. elegans orthologs of the dual oxidase BLI-3and the tetraspanin protein TSP-15, respectively. The C. elegans dual oxidase maturation factor DOXA-1is also required for the arresting effect of excess iodide from RNAi test.We detected in L1animals treated with excess iodide an enhanced biogenesis of reactive oxygen species, which can be suppressed by bli-3or tsp-15mutations.Conclusions:1.Excess iodide causes reversible developmental arrest in C. elegans.2.Loss of functions of the BLI-1/TSP-15/DOXA-1dual oxidase complex suppresses the developmental arrest caused by excess iodide.3.Excess iodide results in an enhanced biogenesis of reactive oxygen species in C. elegans.