Animal models for disease: knockout, knock-in, and conditional mutant mice.

Diseases with a genetic basis can be modeled with knockout, knockin and conditional mutant gene targeted mice. In the following, we provide detailed protocols for gene targeting. Gene targeting of embryonic stem cells can be accomplished by laboratories equipped for tissue culture. Alternatively, many gene targeting services divide the work of targeting with a customer lab. In this collaborative situation, knowledge of the entire process helps ensure a successful outcome. The construction of chimeras for germ line transmission is not described here since this procedure is beyond the means of most laboratories, typically is provided by transgenic core facilities, and is best learned through handson demonstration.