Hypoglycemia can result from multiple causes such as disorders in carbohydrate, fat or amino acid metabolism as well as endocrine system disorders. Since Wwox is expressed in a variety of endocrine, neuroendocrine and non-endocrine tissues it is not possible from these studies to identify the cause of hypoglycemia. The combination of increased BUN with reduced bicarbonate levels suggests impaired CID755673 kidney function and a disturbance in the blood acidbase balance that would result in acidosis. Protracted acidosis disturbs many bodily functions and can lead to growth retardation, bone disease, possibly total kidney failure and ultimately death. Renal tubular acidosis is a pathology that occurs when the kidneys fail to excrete acids into the urine, which causes the blood to remain too acidic due to defects of cells in the proximal and distal convoluted tubules. The convoluted tubules of healthy kidneys help Eupatilin maintain acid-base balance by excreting acids into the urine and returning bicarbonate to the blood. Interestingly, we have previously demonstrated that Wwox is highly expressed in distal convoluted tubules and to a lesser extent in the proximal tubules of the kidney in mice and humans. Given the pathology observed and the location of Wwox expression in the kidney we hypothesize that WWOX may play a role in the regulation of blood pH and maintenance of electrolyte balance. Thus, we speculate that the lack of Wwox expression in the kidney tubules in KO mice is likely responsible for the development of severe metabolic acidosis of renal tubule origin that ultimately leads to death. In addition, as significant contributing factors to morbidity and death, we also observed severe histopathological abnormalities affecting hematopoietic organs such as spleen and thymus in addition to white blood cell counts compatible with a significant suppression on hematopoiesis affecting the Wwox KO mice. Specifically, the spleens of Wwox KO mice displayed signs of atrophy with dramatic reduction in red pulp cellularity. All studies indicate that Wwox KO mice suffered from anemia and leukopenia.