The TAG stop codon was replaced with the T2A-dgCre (DHFR-EGFP-Cre) cassette. Cre recombinase and enhanced green fluorescent protein (EGFP) are expressed under the regulatory control of Calb1 gene elements, without impacting the endogenous expression of the Calb1 gene. The DHFR (dihydrofolate reductase) fragment, derived from the N-terminal 159 amino acids of E. coli ecDHFR, functions as a destabilizing domain (DD). In the absence of specific ligands like TMP (Trimethoprim), this fragment leads to the rapid proteasomal degradation of Cre recombinase. This mechanism allows for the temporal-specific induction of Cre recombinase activity by regulating DHFR-Cre stability with small molecules such as TMP. In addition to studies of Cre recombinase-mediated gene recombination, this model can also be used for EGFP fluorescent protein tracing studies.