Levels of the Na/Pi-IIa cotransporter which serves as the principal mediator of phosphate reabsorption in the kidney can be modulated through post transcriptional or post-translational mechanisms by dietary, hormonal and pharmacological influences. Previous studies have not demonstrated clear cut evidence for modulation of Na/Pi-IIa cotransporter levels through transcriptional mechanisms. We have previously demonstrated that a 4.7kb rat genomic fragment upstream of the rodent Npt2 gene encoding the Na/Pi-IIa cotransporte, is sufficient to mediate its transcriptional activity in vitro. Accordingly, we have established an in vivo experimental model in which this Npt2 genomic fragment fused upstream of a Lac Z reporter gene was expressed as a transgene in mice. The nine independent transgenic founder lines generated, exhibited Lac Z reporter gene expression specifically in the renal cortex. This renal cortical specific expression driven by the Npt2 promoter was confirmed at the mRNA and protein levels using RT-PCR, histochemistry and Lac Z enzymatic activity. Furthermore, the expression of the transgene correlated with expression of the endogenous Npt2 gene during embryonic and early postnatal development. Thus, we have generated a transgenic mouse model which will enable in vivo investigation of the contribution of transcriptional mechanisms to the overall regulation of NaPi IIa expression under physiologic and pathophysiologic conditions.