Cloning and characterization of ZNF236, a glucose-regulated Kruppel-like zinc-finger gene mapping to human chromosome 18q22-q23

We report the cDNA cloning and characterization of ZNF236, a novel Kruppel- like zinc-finger gene initially identified by its glucose-regulated express ion in human mesangial cells using mRNA differential display. Using the dif ferential display fragment as a probe, we screened a human fetal kidney cDN A library and isolated several clones representing two differently spliced mRNA transcripts, designated ZNF236a and -b. Both transcripts were identica l apart from the presence of an additional exon in ZNF236a that truncates t he open reading frame. RT-PCR analysis confirmed the expression of both tra nscripts to be upregulated in human mesangial cells in response to elevated levels of D-glucose. ZNF236a and -b cDNAs encode polypeptides of 174 and 2 04 kDa, containing 25 and 30 C2H2 zinc-finger motifs, respectively. Norther n blot analysis showed that ZNF236 is ubiquitously expressed in all human t issues tested. Expression levels were highest in skeletal muscle and brain, intermediate in heart, pancreas, and placenta, and lowest in kidney, liver , and lung. Southern zoo blot analysis indicated that ZNF236 is conserved i n the genomes of all mammalian species tested, but not in yeast. The mappin g of ZNF236 to human chromosome 18q22-q23, close to the IDDM6 locus, couple d with the glucose-regulated expression of the gene in human mesangial cell s, suggests that ZNF236 may be a candidate gene for diabetic nephropathy. ( C) 1999 Academic Press.