Genetic-Engineered Models of Skeletal Diseases II: Targeting Mutations into Transgenic Mice Chondroc

The manipulation of mice genome is a powerful technique to analyze biological processes that cannot be studied in tissue culture (1 ). The understanding of many developmental processes is today improving because of such techniques. This is also changing the way human genetic diseases are studied. It is now possible to reproduce in laboratory mice the same genetic defects identified in human diseases and, taking species differences into account, to mimic the pathological events that lead to the specific diseases. This allows a developmental, biochemical, and genetic study of human disorders that, for ethical, clinical, or practical reasons, was impossible before. Indeed, the study of genetic diseases of the skeleton has received a great benefit from the generation and the analysis of genetically engineered mutants. However, the availability of such mutants is still limited and considerable effort is required to genetically dissect the pathways that can alter skeletal development. Although such pathways may be very well conserved in Drosophila or Zebrafish, the formation of bone and cartilage is a function acquired later in evolution that cannot be extrapolated from invertebrates and lower vertebrates. These organisms are not the ideal organisms to model human diseases of the skeleton. Therefore, the laboratory mouse is very rapidly becoming the experimental animal of choice to generate mutant animals that carry defects at different checkpoints of cartilage and bone formation (also see Chapters 43 by Jacenko and 45 by Liu, Snead, and Maxson in this volume).