Animal Models of Complex Disorders

The Jacob Lab historically specialized in building and implementing genomic “tools” in the whole animal and continues to develop several of these models. Our goal is to link genomic tools to physiology for discovering the genetic basis of disease, including end stage renal disease (rat and human), hypertension (rat), insulin dependent diabetes mellitus (rat), syndrome-X (rat), left ventricular hypertrophy, myocardial infarction (rat and human) and various cardiac malformations (human). This approach allows us to go from sequence to function using an array of methods to reduce the number of targets to a highly specific list for extensive analyses. In order to reduce the complexity of diseases such as hypertension and diabetes, inbred strains of rats have been bred and their physiology intensively studied. These rat models can then be used to dissect the genetic component of complex diseases. We are actively studying subcongenic strains to identify the genes responsible for causing renal failure, specifically addressing the epistatic role of several gene combinations from subcongenic mapping. At the end of a clinical diagnostic odyssey, these animal models will be crucial for in vivo testing new treatment modality.


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