Mice with targeted gene disruptions or gene insertions for diabetes research: problems, pitfalls, and potential solutions.

The mouse has been a favoured organism for molecular manipulation in studies seeking to establish the genetic bases and pathophysiologic mechanisms underlying both Type I (insulin-dependent) and Type II (non-insulin-dependent) diabetes mellitus. Gene targeting and transgenesis are the two powerful molecular technologies used in these endeavours. Interpretation of results generated from such studies, either entailing an altered phenotype or the absence of a phenotypic change, is not always simple. This review focuses on certain complications inherent in the methodologies, and outlines steps that can be taken to distinguish effects of the genetic manipulation from unexpected contributions from the genetic background.