Expression analysis using oligonucleotide microarrays in mice lacking bradykinin type 2 receptors

We recently conducted detailed cardiovascular and blood pressure-related ph enotypic studies of mice lacking the bradykinin-B-2 receptor and were unabl e to identify a phenotype despite insensitivity to infused bradykinin. We t herefore used oligonucleotide microarray analysis of some 12 000 genes and expressed sequence tags to identify molecular mechanisms that might be invo lved in compensating for the lack of a functional B-2 receptor in the kidne ys of the mice. We identified 2 gene families that may have an impact on ca rdiovascular regulation and the bradykinin pathway. A water transport chann el in the kidney, AQP4, was downregulated in the mice, whereas other member s of the gene family did not show differences in expression levels. In addi tion, a number of serine proteases were upregulated in B-2 receptor- defici ent mice. These genes are all located within a gene cluster on mouse chromo some 7. The findings were verified by an independent method. We suggest tha t microarray analysis has usefulness in elucidating otherwise unappreciated compensatory signaling pathways.