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GENETICALLY ALTERED MOUSE MODELS: THE GOOD, THE BAD, AND THE UGLY

Functional Genomics Unit and Gene Targeting Facility, National Institute of Dental and Craniofacial Research, National Institutes of Health, Building 30, Room 527, 30 Convent Drive, Bethesda, MD 20892;

**corresponding author, akulkarni{at}dir.nidcr.nih.gov

CONTROVERSY This review of the current status of genetically altered mouse models highlights the daunting challenges of untangling complex genetic mechanisms underlying craniofacial development and disease. Although somewhat controversial, largely as a result of technical advances in manipulating the mouse genome, our understanding of craniofacial genetics has broadened substantially. Further advances will open up possibilities for therapeutic interventions by identifying new targets among the plethora of molecular modifiers. — Olav Alvares, Editor

 

Targeted gene disruption in mice is a powerful tool for generating murine models for human development and disease. While the human genome program has helped to generate numerous candidate genes, few genes have been characterized for their precise in vivo functions. Gene targeting has had an enormous impact on our ability to delineate the functional roles of these genes. Many gene knockout mouse models faithfully mimic the phenotypes of the human diseases. Because some models display an unexpected or no phenotype, controversy has arisen about the value of gene-targeting strategies. We argue in favor of gene-targeting strategies, provided they are used with caution, particularly in interpreting phenotypes in craniofacial and oral biology, where many genes have pleiotropic roles. The potential pitfalls are outweighed by the unique opportunities for developing and testing different therapeutic strategies before they are introduced into the clinic. In the future, we believe that genetically engineered animal models will be indispensable for gaining important insights into the molecular mechanisms underlying development, as well as disease pathogenesis, diagnosis, prevention, and treatment.

Key words. Craniofacial development, growth factors, hereditary disease, knockout mice, teeth, transgenic mice

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