Reproducible specificity and efficiency of tamoxifen-mediated cre induction across ages

Temporally controlling cre recombinase through tamoxifen (TAM) induction has many advantages for biomedical research studies. While most projects use TAM induction of mice at early post-natal or adolescence (<2m.o.) ages, age-related neurodegeneration and aging studies can require experimental designs with cre induction in older mice (>12m.o.). While anecdotally reported to be problematic, there are no published comparisons of TAM mediated cre induction at young and older ages. Cx3cr1creERT2 mice for studying microglial were crossed to a floxed NuTRAP reporter to compare cre induction at young (3m.o.) and old (18m.o) ages. Specificity and efficiency microglial labeling was identical at 24m.o. in mice induced with TAM at 3m.o. or 18m.o. of age. Age-related microglial translatomic changes were nearly identical regardless of TAM induction age. While each cre and flox mouse line should be validated before use, these findings demonstrate that TAM induction of cres can be performed even into older mouse ages. Overall design: To investigate the effect of different induction ages on the efficiency, specificity, and usefulness of the Cx3cr1-cre;NuTRAP mouse model. We induced mice at early or late ages, and collected both old and young mice. We used RNA sequencing and flow cytometry to compare the effectiveness of recombination, as well as ability to isolate microglial-specific RNA and detect age related changes.