Lentiviral siRNA Transgenic Rat to Study Vascular Role of Neuropeptide Y

Project Description Narrative:

Hypertension, a major risk factor for stroke and heart and renal disease, affects millions of Americans and escalates healthcare costs. The genetic cause of hypertension is well known. However, identifying the causal genes and understanding the genetic mechanism of this disease is still a daunting task, mainly because of the great heterogeneity of the disease and the technical difficulty of a single gene mutation in the animal model. There is increasing demand for efficient research tools enabling validation of the candidate hypertensive genes. Gene silencing by “knockout” is one of the most informative methods for revealing its function. However, this method cannot be used in the rat, the most comprehensively studied animal model of human hypertension. The goal of this project is to develop an efficient transgenic gene knock-down protocol in the rat using a lentiviral siRNA approach and to examine the effectiveness of this method of gene silencing at the whole animal level.

The long-term goal of the research team is to apply methods of single gene manipulation in the rat to perform integrative physiological studies to better understand the control of blood pressure and to validate candidate hypertension genes.