Polycystic kidney disease (PCKD) is not exactly a household word _except in households where it runs in the family.About one in every 10,000 infants are born with an autosomalrecessive form of PCKD; one in 500 with its dominant version.Enlarged, painful and eventually dysfunctional kidneys mark thisimportant human affliction, in which the recessive trait is lethal tomany perinates, and the dominant can curtail quality and duration oflife for adult sufferers. In PCKD, large numbers of fluid-filled cysts, orbulges, disrupt structure and function of both kidneys.Searching for an animal model to study the chromosomal regions andgene mutations involved in this disease, molecular biologists at the OakRidge National Laboratory in Oak Ridge, Tenn., have generated a lineof transgenic PCK mice, which they describe in the May 27 issue ofScience.Developed by random insertional mutagenesis, they carry a candidatePCK gene, which, as the report's principal author, Richard Woychik,told BioWorld Today, "we think is mimicking the autosomal recessiveform." But, he cautioned, "until we rescue the phenotype, we can't saythat this is solely the gene responsible."Human Equivalent ClonedHe went on to reveal that, "We have since been able to go acrossspecies and clone and characterize the human equivalent _ the humanhomolog, of this mouse gene, mapped to human chromosome 13." Heis currently preparing a manuscript for publication, reporting this latestdevelopment, which should permit, "testing families to determinewhether or not there are any mutations in this gene that are associatedwith renal cystic disease."Woychik's large-scale insertional mutation program at Oak Ridge'sbiology division is "marking a whole variety of mutations besides thePCK trait, including inner ear and skeletal traits."He noted that many of his polycystic mouse models also displaypolydactyly _ double thumbs and big toes _ which occurs as well insome human PCKD patients, depending on the genetic background.The large numbers of out-bulging renal cysts, or pockets, Woychikexplained, "don't happen by hydrostatic pressure, like blowing up aballoon, but rather by local proliferation of epithelial cells in thekidneys' urine collecting ducts. "When you get enough of thesethings," he added, "they put pressure on the normal functioning cellsand you ultimately have a compromised kidney function."This disruption, he observed, " is also interesting because the epitheliallayer is polarized to pump things from the inside out. In PCKD, theypump from outside in." n0602094OAKRIDGE
-- David N. Leff Science Editor
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