Of mice and men: Dissecting the genetic pathway that controls left-right asymmetry in mice and humans

The increasing ability to manipulate the mouse genetically has created a mo del system that is both accessible and an accurate mirror of human developm ent. A combination of analysis of existing spontaneous mouse mutations and creation of targeted mutations has identified at least z24 genes involved i n the specification of mouse left-right asymmetry. These genes function in a carefully orchestrated manner first to create asymmetry at the node, then to signal it to the immediately surrounding cells via the node monocilia, and finally to amplify the initial asymmetry and propagate it to the develo ping organs. Defects at different steps in this pathway result in differenc es in the final phenotype. Human homologues exist for most of the mouse lef t-right determining genes. Notably, when human mutations in these genes hav e been identified in patients with defects of laterality determination, the human phenotype correlates very closely with the corresponding mouse pheno type. Am. J. Med. Genet. (Semin. Med. Genet.) 97:258-270, 2000. (C) 2001 Wi ley-Liss.