Genetic targeting of the endoderm with claudin‐6 CreER

A full description of the ontogeny of the β cell would guide efforts to generate β cells from embryonic stem cells (ESCs). The first step requires an understanding of definitive endoderm: the genes and signals responsible for its specification, proliferation, and patterning. This report describes a global marker of definitive endoderm, Claudin‐6 (Cldn6). We report its expression in early development with particular attention to definitive endoderm derivatives. To create a genetic system to drive gene expression throughout the definitive endoderm with both spatial and temporal control, we target the endogenous locus with an inducible Cre recombinase (Cre‐ER T2 ) cassette. Cldn6 null mice are viable and fertile with no obvious phenotypic abnormalities. We also report a lineage analysis of the fate of Cldn6 ‐expressing embryonic cells, which is relevant to the development of the pancreas, lung, and liver. Developmental Dynamics 237:504–512, 2008. © 2008 Wiley‐Liss, Inc.