title: Analysis of the role of membrane polarity in polycystic kidney disease of transgenic SBM mice.
abstract: Altered membrane polarity has been proposed as an important pathogenetic factor in the development of renal cysts in polycystic kidney disease. To determine whether this alteration in epithelial phenotype is a primary or secondary phenomenon, we examined the epithelial membrane polarity of SBM transgenic mice, in which epithelial proliferation mediated by the c-myc oncogene is an established primary event. Kidneys from 32 transgenic mice and 10 age-matched controls from fetal to adult age were immunostained with antibodies to Na,K-ATPase, fodrin, ankyrin, E-cadherin, and tubule segment-specific lectins. In normal control mice, Na,K-ATPase localization was apical in fetal kidneys but became translocated to the basolateral membrane at maturity. Early microcysts in fetal transgenic kidneys displayed similar (95 to 100%) apical Na,K-ATPase. In young and newborn transgenic mice (1 to 8 days of age), Na,K-ATPase localization was extremely heterogeneous. Noncystic tubules demonstrated either apical (mean 23 to 28%), basolateral (mean 48 to 58%), mixed (mean 4 to 15%), or absent (mean 10 to 13%) staining for Na,K-ATPase. Apical Na,K-ATPase was more frequently observed in early cysts (mean 55%) in young transgenic mice but became less prevalent in adult mice (mean 22%), where 30% of cysts had basolateral staining, 39% mixed patterns, and 9% absent staining. Macrocysts typically lost all Na,K-ATPase reactivity. At all ages, Na,K-ATPase colocalized well with cytoskeletal proteins ankyrin and fodrin. These heterogeneous patterns of Na,K-ATPase staining indicate that although altered cell polarity is frequent in early cystic epithelium of SBM mice, it is not a prerequisite to cystogenesis or progressive cyst enlargement. In conclusion, our results support the view that altered cystic membrane polarity is not a primary process, but represents the persistence of an immature epithelial phenotype characteristic of proliferative polycystic kidney disease epithelia.
mesh_terms: D000818:Animals; D017487:Ankyrins / Q000032:analysis; D000911:Antibodies, Monoclonal / Q000276:immunology; D015820:Cadherins / Q000032:analysis; D002352:Carrier Proteins / Q000032:analysis; D002462:Cell Membrane / Q000502:physiology; D016764:Cell Polarity / Q000502:physiology*; D003598:Cytoskeletal Proteins / Q000032:analysis*; D004848:Epithelium / Q000737:chemistry; D008297:Male; D008565:Membrane Proteins / Q000032:analysis; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008822:Mice, Transgenic; D008840:Microfilament Proteins / Q000032:analysis; D007690:Polycystic Kidney Diseases / Q000737:chemistry* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D000254:Sodium-Potassium-Exchanging ATPase / Q000032:analysis* / Q000276:immunology; D013049:Spectrin
chemical_list: D017487:Ankyrins; D000911:Antibodies, Monoclonal; D015820:Cadherins; D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; D008565:Membrane Proteins; D008840:Microfilament Proteins; D000254:Sodium-Potassium-Exchanging ATPase; D013049:Spectrin