Genetic targeting of the endoderm with claudin-6CreER.
A full description of the ontogeny of the beta cell would guide efforts to generate beta 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.
Anderson
William J
WJ
Department of Molecular and Cellular Biology, Howard Hughes Medical Institute, Harvard Stem Cell Institute, Harvard University, Cambridge, Massachusetts 02138, USA.
Zhou
Qiao
Q
Alcalde
Victor
V
Kaneko
Osamu F
OF
Blank
Leah J
LJ
Sherwood
Richard I
RI
Guseh
J Sawalla
JS
Rajagopal
Jayaraj
J
Melton
Douglas A
DA
D000818:Animals; D019070:Cell Lineage / Q000235:genetics / Q000502:physiology*; D057167:Claudins; D017931:DNA Primers / Q000235:genetics; D004707:Endoderm / Q000196:embryology* / Q000378:metabolism*; D005697:Galactosides; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D005838:Genotype; D017403:In Situ Hybridization; D007211:Indoles; D019426:Integrases / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D020133:Reverse Transcriptase Polymerase Chain Reaction
D057167:Claudins; D017931:DNA Primers; D005697:Galactosides; D007211:Indoles; D008565:Membrane Proteins; C045073:Cre recombinase; D019426:Integrases; C122101:claudin 6; C044888:5-bromo-4-chloro-3-indolyl beta-galactoside