CDNA CLONING AND LOCALIZATION OF OCRL-1 IN RABBIT KIDNEY

The oculocerebrorenal syndrome of Lowe (OCRL) is a hereditary multisys tem disorder characterized by congenital cataracts, mental retardation , renal tubular dysfunction, and progressive renal insufficiency. Tubu lar abnormalities include proximal tubular dysfunction, a distal acidi fication defect, and a possible impairment of urinary concentrating ab ility. The most important renal manifestation of Lowe's syndrome is a progressive loss of kidney function associated with a glomerular lesio n that progresses to end-stage renal disease in either the third or fo urth decade. The gene responsible for Lowe's syndrome, OCRL-1, was rec ently identified by positional cloning, and mutations were demonstrate d in many affected patients. In the present study reverse transcriptio n-polymerase chain reaction (RT-PCR) was used to clone a partial-lengt h cDNA encoding rabbit renal OCRL-1. There is a high degree of similar ity between rabbit and human sequences, with nucleotide and amino acid identities of 92% and 97%, respectively. Northern analysis identified a 5.4-kb transcript that is expressed in bath rabbit kidney cortex an d medulla. Isolated nephron-segment RT-PCR showed that OCRL-1 is expre ssed in all segments studied: the glomerulus, proximal tubule, medulla ry and cortical thick ascending limb, distal convoluted tubule, connec ting tubule, cortical collecting duct, and outer medullary collecting duct. Defective OCRL-1 expression in these regions may play a pathogen etic role in the renal manifestations of this syndrome.