Mesodermal specific cDNA or transcript (MEST) was identified by suppression subtractive hybridization-PCR of cDNA isolated from embryonic day-13 versus newborn mice kidneys. At day-13 of mouse gestation, a high expression of MEST with single ~2.7 kb size transcript was observed, which was exclusively localized to the metanephric mesenchyme. The MEST mRNA expression gradually decreased during the later stages, followed by an abrupt decrease in the newborn kidneys and subsequent postnatal life, after which a very mild expression persisted in the glomerular mesangium. The regression in the mRNA expression during embryonic renal development appears to be related to methylation of the MEST gene. Treatment of metanephroi, harvested at day-13 of gestation, with MEST-specific antisense oliogodeoxynucleotide resulted in a dose-dependent decrease in size of the explants and nephron population. This was associated with a selective decrease of MEST mRNA expression and accelerated apoptosis of the mesenchyme. These findings suggest that MEST, a gene with a putative mesenchymal-derived protein, conceivably plays a role in mammalian metanephric development.