Nuclear receptors (NRs) compose a large family of transcription factors that operate at the interface between genes and environment, acting as sensors and effectors that translate endocrine and metabolic cues into well-defined gene expression programs. We report here on a systematic quantitative and anatomical expression atlas of the 49 NR genes in 104 regions of the adult mouse brain, organized in the interactive MousePat database. MousePat defines NR expression patterns to cellular resolution, a requirement for functional genomic strategies to understand the function of a highly heterogeneous and complex organ such as the brain. Using MousePat data, NR expression patterns can be clustered into anatomical and regulatory networks that delineate the role of NRs in brain functions, like the control of feeding and learning/memory. Mining the MousePat resource will improve the understanding of NR function in the brain and elucidate hierarchical networks that control behavior and whole body homeostasis.

We defined the intestinal nuclear hormone receptor map, which indicates that the localization pattern of a receptor in normal intestine predicts the modulation of its expression in tumors. Our results are useful to select those nuclear receptors that could be used eventually as early diagnostic markers or targeted for clinical intervention in intestinal polyposis and cancer.

Site-specific recombination systems are widespread and popular tools for all scientists interested in manipulating the mouse genome. In this chapter, we focus on the use of site-specific recombinases (SSR) to unravel the function of genes of the mouse. In the first part, we review the most commonly used SSR, Cre and Flp, as well as the newly developed systems such as Dre and PhiC31, and we present the inducible SSR systems. As experience has shown that these systems are not as straightforward as expected, particular attention is paid to facts and artefacts associated with their production and applications to study the mouse genome. In the next part of this chapter, we illustrate new applications of SSRs that allow engineering of the mouse genome with more and more precision, including the FLEX and the RMCE strategies. We conclude and suggest a workflow procedure that can be followed when using SSR to create your mouse model of interest. Together, these strategies and procedures provide the basis for a wide variety of studies that will ultimately lead to the analysis of the function of a gene at the cellular level in the mouse.