Over-expression of adenosine deaminase in mouse podocytes does not reverse puromycin aminonucleoside resistance

A mouse line expressing functional ADA under the control of the podocyte-specific podocin promoter was generated by transgenesis. The effect of PAN on urinary excretion of sodium and proteins was compared in rats and in mice over-expressing ADA and in littermates.We confirmed that expression of ADA mRNAs was much lower in wild type mouse than in rat glomerulus. Transgenic mice expressed ADA specifically in the glomerulus, and their ADA activity was of the same order of magnitude as in rats. Nonetheless, ADA transgenic mice remained insensitive to PAN treatment in terms of both proteinuria and sodium retention.Along with previous results, this study shows that adenosine deaminase is necessary but not sufficient to confer PAN sensitivity to podocytes. ADA transgenic mice could be used as a background strain for further transgenesis.Nephrotic syndrome is defined by abnormal urinary excretion of proteins leading to hypoalbuminemia. These biological signs are secondary to alterations of the glomerular filtration barrier. The primary forms of the disease correspond to either genetic alterations of proteins involved in the glomerular filtration barrier or to the idiopathic nephrotic syndrome which is due to a circulating factor that functionally alters the glomerular barrier. Whatever its etiology, nephrotic syndrome is always associated with renal retention of sodium which, along with alterations of the permeability properties of the capillary wall, promotes ascites and/or edema [1]. The most widely used animal model to study sodium retention in nephrotic syndrome is a rat model that reproduces the biological and clinical signs of the human disease [2,3]. It is induced by a single injection of puromycin aminonucleoside (PAN), an adenosine derivative used as an antibiotics and anti-proliferative drug that also induces nephrotic syndrome in humans.Previous studies in nephrotic rats have shown that sodium retention results from stimulation of its reabsorption in the aldoster