The present invention isolates and characterizes the exc-4
gene of C. elegans, and identifies exc-4 as an orthologue of the human CLIC family of
chloride intracellular channels. Accordingly, a
nucleic acid having the sequence of SEQ ID NO.: 1 is disclosed, as well as recombinant vectors and host cells comprising the
nucleic acid sequence of SEQ ID NO.: 1. Further, a number of screening methods are disclosed to identify putative agents that inhibit
vertebrate, and preferably human, CLICs using C. elegans and exc-4 inhibition as a loss-of-
function model for CLIC activity. Also disclosed is a method of determining whether a specific member of the CLIC
gene family is involved in tubulogenesis, where the rescue of a C. elegans exc-4 excretory
cell phenotype via expression of a transgenic CLIC
gene of interest indicates that the CLIC gene of interest is involved in tubulogenesis. Finally, a method is disclosed of identifying putative
vertebrate, and preferably human, CLIC inhibitors using transgenic C. elegans exc-4
mutant embryos, where expression of the
transgene yields a CLIC product that rescues the exc-4
mutant phenotype. Agents of interest resulting in a reversionary exc-4
mutant phenotype are putative agents that inhibit CLIC expression or function.