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

ABSTRACT: 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.

ORGANISM(S): Mus musculus

PROVIDER: GSE241574 | GEO | 2023/12/14

REPOSITORIES: GEO

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Cx3Cr1-Cre induction leads to microglial activation and IFN-1 signaling caused by DNA-damage in early postnatal brain

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Transcription profiling of mouse with unilateral cochlear removal in Cochlear Nucleus at P7 and P21

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2008-06-13 | E-GEOD-5394 | biostudies-arrayexpress

Gene Expression after Cochlear Removal in Cochlear Nucleus at P7 and P21

Project description:Deprivation of peripheral nerve input by cochlear removal in young mice results in dramatic neuron death in the cochlear nucleus (CN). The same manipulation in older mice does not result in significant loss. The molecular basis of this critical period of vulnerability remains largely unknown. Here we identified genes regulated at early time points after cochlear removal at ages when neurons are vulnerable (postnatal day (P)7) or invulnerable (P21) to this challenge. Afferent deprivation regulated very different sets of genes at P7 and P21. These genes showed a variety of functions at both ages, but surprisingly there was no net increase in pro-apoptotic genes at P7. A large set of upregulated immune-related genes was identified at P21. Keywords: Time Course after Cochlear Removal, Age Comparison

2007-12-26 | GSE5394 | GEO

Tamoxifen induction of Cre recombinase does not cause long lasting or sexually divergent responses in the CNS epigenome or transcriptome: implications for the design of aging studies (RNA-Seq).

Project description:The systemic delivery of tamoxifen (Tam) to activate inducible CreERT2-loxP transgenic mouse systems is now widely used in neuroscience studies. This critical technological advancement allows temporal control of DNA-cre recombination, avoidance of embryonically lethal phenotypes, and minimization of residual cell labeling encountered in constitutively active drivers. Despite its advantages, the use of Tam has the potential to cause long-lasting, uncharacterized side effects on the transcriptome and epigenome in the CNS, given its mixed estrogen receptor (ER) agonist/antagonist actions. With the welcome focus on including both sexes in biomedical studies and efforts to understand sex differences, Tam administration could also cause sexually divergent responses that would confound studies. To examine these issues, epigenetic and transcriptomic profiles were compared in C57BL/6J female and male hippocampus, cortex, and retina 1 month after a five- day Tam treatment typical for cre induction, or vehicle control (sunflower seed oil). Cytosine methylation and hydroxymethylation levels, in both CG and non-CG contexts, were unchanged as determined by oxidative bisulfite sequencing. Long-lasting Tam transcriptomic effects were also not evident/minimal. Furthermore, there is no evidence of sexually divergent responses with Tam administration and Tam did not alter sex differences evident in controls. Combined with recently reported data that Tam alone does not cause long-lasting changes in behavior and neurogenesis, our findings provide confidence that Tam can be used as a cre-recombinase inducer without introducing significant confounds in transcriptomic and epigenomic neuroscience studies, particularly those focused on genomic and transcriptomic aspects of the aging brain.

2019-08-13 | GSE135752 | GEO