A practical guide to genetic engineering of pancreatic β-cells in vivo: getting a grip on RIP and MIP

In vivo gene manipulation is a cornerstone approach in modern physiology. Cre-Lox technology has been extensively used to delete genes and activate reporters in pancreatic β-cells, bringing new insight into the pathophysiology of diabetes. In all cases, it is important to understand the expression domain of the specific reporter-Cre combination in order to correctly interpret the data. In the case of targeted genes with significant expression and function in the brain, the use of Ins2 promoter driven Cre, commonly known as RIP-Cre, has been shown to confound data interpretation when appropriate controls are not present. The recent article from the Philipson group in Islets provides an important characterization of a new Cre-deleter model, referred to as MIP1-CreER, which employs the mouse Ins1 promoter. This Ins1 promoter, recapitulating the expression pattern of the endogenous Ins1 gene, does not drive significant transgene expression in the brain and therefore is highly specific for deleting genes or turning on reporters in the pancreatic β-cell. This model promises to be widely used in the field of islet biology. Here, I review recent developments in the area of in vivo gene modification and predict areas where such tools will be refined further.