Mouse mutants that perturb cortical patterning, such as reeler, have provided considerable insight into the development of the mammalian brain. We have previously undertaken a project to generate models of human congenital defects by screening ENU-mutagenized mice for recessive mutations affecting late embryonic development. The screen incorporated a genetic mapping component, which has facilitated the positional cloning and functional characterization of the mutant genes. The strategy has worked well, and we have generated many mice with phenotypes similar to human malformation syndromes and birth defects. In this proposal we aim to target cortical development, with the goal of identifying and cloning additional mutants that will be useful for understanding how the mammalian brain is patterned. The Specific Aims of this project are: 1) to screen for mutations affecting neurodevelopment in ENU-mutagenized mice; 2) to positionally clone the affected genes in mice carrying developmental mutations, and 3) to molecularly characterize the developmental defects in mutant mice.
