Fig. 1. Generation of a CREB mutation selective for sympathetic neurons. (A) Schematic representation of the DBHiCre PAC used for transgenesis. The linear insert of 150 kb carrying the transgene construct contains approximately 100 kb upstream of the ATG of the Dbh gene. (B) Detection of DBHCre activity at E11.5 in the reporter mouse line ROSA26 by whole-mount ß-galactosidase staining in sagittal sections at different levels of the sympathetic chain, from rostral to caudal (i), (ii) and (iii). Adjacent sagittal sections from E12.5 control (Creb^fl/fl) and mutant (Creb^DBHCre) embryos are stained with anti-DBH (C,F), anti-Cre (D,G) and anti-CREB (E,H) antibodies. At E12.5, DBH expression characterizes sympathetic precursors in control (C) and mutant (F) embryos. In control Cre-negative precursors, CREB protein is present (D,E), whereas Cre-positive cells lose CREB immunoreactivity in the conditional mutants (G,H). Scale bar: 2 mm in B; 130 µm in C-H.