Mice, microarrays, and the genetic diversity of the brain

Open Access
Publisher Website
Google Scholar
Abstract
Technological advances in molecular biology and genetics have allowed neuroscientists to reduce the study of the brain to individual proteins or genes of interest. The challenge of making the jump from such detailed molecular study to an integrated understanding of brain structure or function is highlighted by the large number of genes and combinations of genes and the time necessary to study the function of any one gene product individually. These same advances in molecular biology that have propelled our knowledge of neuronal development and functioning over the last decade have also widened an implicit division between molecular and systems neuroscientists. cDNA microarray technology offers the exciting potential to bridge the molecular-systems gap by allowing for a systems-level molecular or “genomic” approach to neurobiology because of its unprecedented capacity to monitor simultaneously widespread changes in gene expression. The parallel monitoring of thousands of genes provides a more global view of the system being studied than classic reductionist techniques and requires sophisticated quantitative analytic and computational approaches that are not currently available at the bench of the typical molecular neurobiology lab. Despite some of the barriers to entry, microarray expression profiling is one of several genetic approaches that will have a broad and lasting impact on our molecular and systems understanding of brain development and functioning. Two basic platforms for fluorescent microarray expression studies currently exist—oligonucleotide arrays and spotted cDNA arrays (Fig. 1; refs. 1 and 2). In this issue of PNAS, Sandberg et al. (3) have elegantly applied microarray expression profiling by using oligonucleotide arrays (4, 5) to begin to map out the baseline differences in gene expression that may underlie structural and behavioral differences between inbred laboratory mouse strains. Over 400 inbred mouse strains with known genealogy exist, and their power for the dissection of complex behavioral …