Towards an ovine model of cystic fibrosis

As little as five years ago, the idea that it would be possible to generate an ovine model of cystic fibrosis (CF) was frequently met with humour and disbelief. Fortunately for those of us attempting to produce a large animal model of this debilitating disease, the generation of cloned sheep ( 1,2) changed all of that. The case must now be made for the production of an ovine model for CF. The justification may be applied to large animal models of many other human genetic diseases. Recent data showing that the cloning technology is applicable to other species, such as the cow (3), provide further support for the feasibility of this approach. The use of animal models of human disease has been fundamental to elucidating the pathological mechanisms of many disorders. A number of well characterized, naturally occurring animal models of human genetic diseases exist. In addition, the relative ease and efficiency of the mouse ‘gene knockout’ technology has transformed the possibilities of generating animal models of specific monogenic disorders. However, mouse knockout models vary in their similarity to human disease. A number of strains of CF mice have been generated that carry different mutations ( 4–13), but none of them have cystic fibrosis, a disease primarily characterised by recurrent lung infection and pancreatic destruction. CF mice have normal pancreatic function and little airway disease in a limited life span. Instead, the majority of strains die from intestinal obstruction. There is no doubt that the CF mice have been extremely useful in addressing a number of questions relating to CF disease mechanisms; however, their limitations are now restricting progress.