BAC Transgenic Mice and the GENSAT Database of Engineered Mouse Strains

Abstract

The brain is a complex tissue comprising hundreds of distinct cell types, each of which has unique circuitry and plays a discrete role in nervous system function. Large-scale studies mapping gene-expression patterns throughout the nervous system have revealed that many genes are exclusively expressed in specific cell populations. The GENSAT (Gene Expression Nervous System Atlas) Project created a library of engineered mice utilizing bacterial artificial chromosomes (BACs) to drive the expression of enhanced green fluorescent protein (eGFP) in genetically defined cell populations. BACs contain large segments of genomic DNA and retain most of the transcriptional regulatory elements directing the expression of a given gene, resulting in more faithful reproduction of endogenous expression patterns. BAC transgenic mice offer a robust solution to the challenging task of stably and reproducibly accessing specific cell types from a heterogeneous tissue such as the brain. A significant advantage of utilizing eGFP as a reporter is the fact that it can fill entire cells, including neuronal dendrites and axons as well as glial processes, making GENSAT reporter mice a powerful tool for neuroimaging studies. This article provides a primer on the generation of BAC transgenic mice and advantages for their use in labeling genetically defined cell types. It also provides an overview of searching the GENSAT database and ordering engineered mouse lines.