Bc. Erb et al., CDNA CLONING AND LOCALIZATION OF OCRL-1 IN RABBIT KIDNEY, American journal of physiology. Renal, fluid and electrolyte physiology, 42(5), 1997, pp. 790-795
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.