The kidney is the organ in vertebrates chiefly responsible for eliminating wastes from the blood and regulating the blood’s chemical balance. The anatomy of the kidney and the architecture of the cells that compose it are related to its function.
The glomerulus is the structure in the kidney that filters blood. The major filtration surface of the glomerulus consists of a basement membrane covered by fenestrated endothelial cells and specialized epithelial cells, called podocytes. Podocytes have delicate interdigitating foot processes that cover the exterior basement membrane surface of the glomerular capillary. Podocytes are responsible in part for the charge and size filtration characteristics of the glomerulus.
When a dysfunction of glomerular filtration occurs, proteins from the blood can leak into the urine and illness and death can result. The major anatomic abnormality associated with this dysfunction is effacement, or fusion, of the podocyte foot processes. The molecular mechanisms underlying these dysfunctions are not well understood.
Thus, there exists a need for identifying the molecular defects associated with the gross pathological changes that occur in kidney disease and for developing methods for identifying and treating the molecular defects. The present invention satisfies these needs and provides related advantages as well.
The invention provides isolated mammalian GLEPP1 proteins such as human GLEPP1 protein and rabbit GLEPP1 protein. The invention also provides isolated polypeptides comprising a protein tyrosine phosphatase (PTPase) domain of a mammalian GLEPP1 protein. In addition, the invention provides antibodies specific for a mammalian GLEPP1 protein.
The invention further provides isolated nucleic acid sequences encoding a mammalian GLEPP1 protein or a PTPase domain of a mammalian GLEPP1 protein. The invention also provides vectors that can express a nucleic acid sequence encoding a mammalian GLEPP1 protein. In addition, the invention provides host cells that contain the vectors and express the polypeptide. The invention also provides nucleic acid probes having a nucleotide sequence corresponding to a portion of a mammalian GLEPP1 gene such as the human GLEPP1 gene and the rabbit GLEPP1 gene.
The invention further provides methods of detecting the presence of a glomerular pathology in a subject comprising detecting an abnormally low level of GLEPP1 mRNA or GLEPP1 protein expression in a podocyte. The invention also provides methods of detecting a glomerular pathology comprising detecting the presence of a defective GLEPP1 gene in a subject. In addition, the invention provides methods of treating a glomerular pathology characterized by an abnormally low level of expression of GLEPP1 protein comprising introducing a nucleic acid molecule encoding a normal mammalian GLEPP1 protein or a PTPase domain of a mammalian GLEPP1 protein into a subject and expressing the normal protein or domain.