Rescue of Fanconi Bickel Syndrome by targeting glucose transport in the renal proximal tubule

Fanconi Bickel Syndrome (FBS) is a rare genetic disease due to homozygous or compound heterozygous mutations of GLUT2 gene. This gene encodes for a protein that allows the final absorption of glucose from the pre-urine to the blood stream. FBS patients suffers of life-threating electrolytes and acid-base imbalance causing, in addition, severe bone alterations. These clinical features are secondary to the dysfunction of a part of the kidneys called proximal tubule. Currently, there is no therapy for these patients, beside the replacement of the substances loss in the urines. Therefore, the molecular mechanisms underlying the role of the GLUT2 and the single functions of the PT cells are completely unknown. This strongly interferes with the possibility of building up an efficacious therapeutic approach. Given that, this study aims to generate an experimental mouse model of FBS, that recapitulates the human disease. This model will be useful to identify the physiopathologic link between the GLUT2 and the main transporters involved in the electrolytes and other small molecules handled by the PT. In addition, this study aims to directly investigate, in this experimental model, a novel pharmacological approach able to restore the glucose homeostasis in the cells of the PT and so to improve the overall function of this segment and rescue the disease