The Cck-CreER (or Cck-CreERT2) knock-in allele both abolishes cholecystokinin (Cck) gene function and expresses the CreERT2 fusion protein from the Cck promoter/enhancer elements. The donating investigator reports that homozygous mice are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. Homozygotes may be expected to have a phenotype similar to other null mutations of this gene and may exhibit metabolic abnormalities of the endocrine/exocrine glands (increased pancreatic amylase).
Cre-ERT2 fusion gene activity is inducible; observed following tamoxifen administration. As such, when Cck-CreERT2 mice are bred with mice containing loxP-flanked sequences, tamoxifen-inducible Cre-mediated recombination will result in deletion of the floxed sequences in the Cck-expressing cells of the offspring. These Cck-CreERT2 mice may be useful in studying brain anatomy, physiology and behavior.
The donating investigator reports tamoxifen-inducible Cre recombinase activity recapitulates the endogenous Cck expression pattern, with moderate efficiency of induction. They report tamoxifen-inducible Cre recombinase activity is not observed prior to tamoxifen treatment. Following tamoxifen administration, Cre recombinase activity is observed in cholecystokinin positive neurons in cortex (both interneurons and pyramidal neurons). The donating investigators did not examine cre expression in subcortical neurons or in any tissues other than brain.
For characterization information, see images at the Allen Institute for Brain Science website (Cck-CreERT2 images).
The Cre-ERT2 fusion protein consists of Cre recombinase fused to a triple mutant form of the human estrogen receptor which does not bind its natural ligand (17β-estradiol) at physiological concentrations but will bind the synthetic estrogen receptor ligands 4-hydroxytamoxifen (OHT or tamoxifen) and, with lesser sensitivity, ICI 182780. Restricted to the cytoplasm, Cre-ERT2 can only gain access to the nuclear compartment after exposure to tamoxifen. To counteract the mixed estrogen agonist effects of tamoxifen injections, which can result in late fetal abortions in pregnant mice, progesterone may be coadministered.
