IDENTIFICATION OF PKDL, A NOVEL POLYCYSTIC KIDNEY-DISEASE 2-LIKE GENEWHOSE MURINE HOMOLOG IS DELETED IN MICE WITH KIDNEY AND RETINAL DEFECTS

Polycystin-1 and polycystin-2 are the products of PKD1 and PKD2, genes that are mutated in most cases of autosomal dominant polycystic kidne y disease. Polycystin-2 shares similar to 46% homology with pore-formi ng domains of a number of cation channels. It has been suggested that polycystin-2 may function as a subunit of an ion channel whose activit y is regulated by polycystin-1, Here we report the identification of a human gene, PKDL, which encodes a new member of the polycystin protei n family designated polycystin-L, Polycystin-L has 50% amino acid sequ ence identity and 71% homology to polycystin-2 and has striking sequen ce and structural resemblance to the pore-forming alpha 1 subunits of Ca2+ channels, suggesting that polycystin-L may function as a subunit of an ion channel. The full-length transcript of PKDL is expressed at high levels in fetal tissues, including kidney and liver, and down-reg ulated in adult tissues. PKDL was assigned to 10q24 by fluorescence in situ hybridization and is linked to D10S603 by radiation hybrid mappi ng. There is no evidence of linkage to PKDL in six ADPKD families that are unlinked to PKD1 or PKD2, The mouse homologue of PKDL is deleted in Krd mice, a deletion mutant with defects in the kidney and eye. We propose that PKDL is an excellent candidate for as yet unmapped cystic diseases in man and animals.