Ksp-cadherin gene promoter. II. Kidney-specific activity in transgenic mice

Kidney-specific cadherin (Ksp-cadherin, cadherin 16) is a tissue-specific m ember of the cadherin superfamily that is expressed exclusively in the baso lateral membrane of tubular epithelial cells in the kidney. To determine th e basis for tissue-specific expression of Ksp-cadherin in vivo, we evaluate d the activity of the promoter in transgenic mice. Transgenic mice containi ng 3.3 kb of the mouse Ksp-cadherin promoter and an Escherichia coli lacZ r eporter gene were generated by pronuclear microinjection. Assays of beta-ga lactosidase enzyme activity showed that the transgene was expressed exclusi vely in the kidney in both adult and developing mice. Within the kidney, th e transgene was expressed in a subset of renal tubular epithelial cells tha t endogenously expressed Ksp-cadherin and that were identified as collectin g ducts by colabeling with Dolichos biflorus agglutinin. In the developing metanephros, expression of the transgene in the branching ureteric bud corr elated with the developmental expression of Ksp-cadherin. Identical pattern s of expression were observed in multiple founder mice, indicating that kid ney specificity was independent of transgene integration site. However, het erocellular expression was observed consistent with repeat-induced gene sil encing. We conclude that the Ksp-cadherin gene promoter directs kidney-spec ific expression in vivo. Regulatory elements that are sufficient to recapit ulate the tissue- and differentiation-specific expression of Ksp-cadherin i n the renal collecting duct are located within 3.3 kb upstream to the trans criptional start site.