Clearance Studies in Genetically Altered Mice

Measurements of renal clearance, including the measurement of the glomerular filtration rate (GFR), renal plasma flow (RPF), and electrolyte excretion rate, form the foundation for evaluating kidney function in the intact organism. Although much of our current knowledge regarding the kidney was developed using classical in vivo clearance approaches in larger animals such as dogs and rats, new molecular approaches for producing targeted gene mutations in mice have led to a renewed interest in evaluating kidney function at the level of the whole animal. Our understanding of renal physiology and the molecular mechanisms of blood-pressure regulation and extracellular fluid (ECF) volume homeostasis by the kidney has been significantly advanced as transgenic and gene-knockout mouse models have become available. This chapter focuses on special considerations for applying clearance methods in the mouse, with the idea that adapting mouse methodologies and techniques for use in larger animals (such as the rat) is simpler than adapting large animal methods for use in the mouse. In developing and adapting techniques appropriate for the mouse, it became apparent that mice are more sensitive to stress than rats, and it was clear that the technical refinement of existing methodologies would be necessary to reliably reproduce experiments in the mouse. Over the past several years, significant advances have been made in the technologies available for evaluating renal physiology in the mouse.