ABSTRACT
Preclinical safety testing and checks for absence of toxicity or germ-line transmission can be carried out using normal animals while gene delivery can be evaluated by introducing reporter genes into normal animals. The development of functional and safe somatic gene therapy protocols is key to the success of this approach to treat inherited disease. Different founder animals will have different numbers of transgenes integrated at different chromosomal sites which will modulate transgene expression. Providing that the gene responsible has been cloned, it is possible to generate homozygous mutant mice by gene targeting in pluripotent embryonic stem cells. Animal models have proved crucial in assessing the feasibility of gene therapy strategies for cystic fibrosis. The cftr mutant mice have proved to be very useful in assessing gene therapy protocols, but one obvious limitation of the model is the lack of lung disease.
