Renal abnormalities in mice caused by insufficiency of p38alpha

p38MAP kinase (p38) is activated by hypertonicity and has been implicated to play a pivotal role in the renal system in survival under hypertonic conditions, both in vitro and in vivo. Although there are many aspects of the molecular events via the p38 pathway, its contribution to renal physiology and pathophysiology remains unclear. To elucidate the physiological relevance of p38 in renal function, we performed histochemical and biochemical characterization of p38alpha+/- mice. Although p38alpha+/- mice appeared normal, they showed 24% higher water intake (P < 0.05) and 16% higher kidney weight to total body weight ratio (P < 0.01) at 21 weeks of age. Histological examination of the kidney showed abnormalities such as dilation of proximal convoluted tubules, vacuolar degeneration, focal interstitial fibrosis, and inflammation and enlargement of Bowman's capsule with advancing age. Taken together, these results suggest that p38alpha plays an important role in the structural and functional maintenance of the normal kidney and its insufficiency causes renal abnormalities.