Induced mouse chromosomal rearrangements as tools for identifying critical developmental genes and pathways

Due to the rapid advances that have been made in molecular and genetic technology during the past decade, the genes associated with a large number of human hereditary diseases have been isolated and analyzed in detail. These cloned genes provide new tools for research geared toward a better understanding of normal human development, and also of the many ways that basic, essential morphologic pathways can be disturbed. Chromosomal rearrangements, especially deletions and translocations, have been especially beneficial in the mapping and isolation of human disease genes because of their visibility on both the cytogenetic and molecular levels. However, these useful types of mutations occur with low frequency in the human population. Chromosomal rearrangements can be induced relatively easily in mice, and several large, independent collections of translocation and deletion mutants have been generated in the course of risk-assessment and mutagenesis studies over the past several decades. Combined with new molecular technologies, these collections of mutant animals provide a means of gaining ready access to genes associated with developmental defects including craniofacial abnormalities, hydrocephaly, skeletal deformities, and complex neurologic disorders. As an illustration of this approach, we briefly review our progress in the study of three mutations associated with defects in palate development, juvenile growth, fitness and sterility, and neurologic development in mice, respectively.