Analysis of mammalian central nervous system gene expression and function using bacterial artificial chromosome-mediated transgenesis

The anatomical complexity of the mammalian central nervous system (CNS) pre sents special problems for the analysis of CNS gene expression and function . The most difficult challenge is presented by the simple fact that there a re hundreds of functionally and morphologically defined cell types in the C NS. Given this complexity, the interpretation of CNS phenotypes is often pr oblematic. The preparation of transgenic mice carrying marked bacterial art ificial chromosomes (BACs) provides an important avenue for improving our u nderstanding of CNS-expressed genes and phenotypes. This approach can allow efficient analysis of patterns of gene expression, subcellular localizatio n of their encoded products and neuronal projection patterns. BAC transgeni c mice can also provide access to information relevant to gene function bas ed on phenotypes arising from increased gene dosage or expression of activa ting and dominant-negative alleles. This review will concentrate on these i ssues and their relevance to the analysis of CNS-expressed genes.