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

Area of Science:

• Cardiovascular Physiology
• Molecular Biology
• Renal Physiology

Background:

• Cardiovascular and blood pressure studies in mice lacking the bradykinin-B(2) receptor revealed no discernible phenotype.
• Mice lacking the bradykinin-B(2) receptor were insensitive to infused bradykinin, suggesting compensatory mechanisms may be active.

Purpose of the Study:

• To identify molecular mechanisms compensating for the lack of a functional bradykinin-B(2) receptor in the kidneys of mice.
• To investigate potential impacts on cardiovascular regulation and the bradykinin pathway.

Main Methods:

• Oligonucleotide microarray analysis of approximately 12,000 genes and expressed sequence tags.
• Verification of findings using an independent method.

Main Results:

• Downregulation of the water transport channel aquaporin-4 (AQP4) in the kidneys of B(2) receptor-deficient mice.
• Upregulation of several serine proteases in B(2) receptor-deficient mice.
• Identified gene families impacting cardiovascular regulation and the bradykinin pathway, located on mouse chromosome 7.

Conclusions:

• Microarray analysis is a valuable tool for uncovering compensatory signaling pathways.
• The kidneys exhibit compensatory gene regulation in response to the absence of a functional bradykinin-B(2) receptor.