Renal tubular cells cultured from genetically modified animals

The culture of renal tubular cells from genetically modified animals opens the opportunity of biochemical, cell biology and physiological studies unde r strictly controlled conditions. Either primary cultures or cell lines can be used. Through two examples of primary cultures of proximal tubular cell s obtained from knock-out mice, important information about the function of proteins were obtained. Mice lacking vimentin, an intermediate filament no rmally reexpressed in tubular cells during regeneration and culture, have a normal tubular function under basal conditions. Proximal cells grown from these animals exhibit a defect in sodium-glucose cotransport activity, most likely related to alterations in the dimer/monomer ratio of the transporte r in the apical membranes. These alterations may be important in terms of t ubular function during the recovery phase following acute tubular necrosis. The situation is strikingly different with regard to mice lacking HNF-1, a transactivator involved in the transcription of multiple genes. These anim als suffer from severe Fanconi syndrome related to decreased expression of proximal transporters including isoforms of sodium-glucose (SGLT2) and sodi um-phosphate (NPT1) cotransporters. Whereas transport defects are observed in isolated tubules, they are no longer apparent in cultured proximal cells because the expression of these isoforms is suppressed under culture condi tions. These observations illustrate the interest and limits of the in vitr o models for studying renal function in transgenic animals. Copyright (C) 1 999 S. Karger AG, Basel.