PMC:1189073 / 1502-3076 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/1189073","sourcedb":"PMC","sourceid":"1189073","source_url":"http://www.ncbi.nlm.nih.gov/pmc/1189073","text":"Nephrogenic diabetes insipidus (NDI) is a disease marked by excessive urination and thirst. Normally, the hypothalamus senses situations where water is limited and signals to the kidney to increase water reabsorption from urine. The signaling molecule secreted by the hypothalamus is arginine vasopressin (AVP), which binds to a specific protein on the surface of kidney cells, AVP receptor (AVPR2). AVP binding to its receptor on kidney cells begins a series of biochemical events that ultimately results in the insertion of a protein, aquaporin 2 (AQP2), into the outer surface of the kidney cell. As its name suggests, AQP2 facilitates the reuptake of water from the urinary space into the cell, thus concentrating the urine and conserving water. Congenital NDI is caused by mutations in either the water channel, AQP2, or in the receptor, AVPR2. While these mutations have been studied extensively in the lab, work in live animals has been very limited. This report describes the first viable mouse model of NDI. Previous models have been attempted by targeted mutation, i.e., genes known to be involved in the disease have been altered in the mouse, a so-called reverse genetic approach. Reverse genetic approaches have so far failed to produce a viable mouse model of NDI. Here the authors take a forward genetic approach in which genes are mutated at random and animals are screened for disease-like properties. As well as proving hypotheses that come from lab studies, this model opens the door to the testing of gene therapy or other therapies for treatment of NDI.","tracks":[]}