Specificity and efficiency of tamoxifen-mediated Cre induction is equivalent regardless of age

Collyn M Kellogg; Kevin Pham; Sunghwan Ko; Jillian E J Cox; Adeline H Machalinski; Michael B Stout; Amanda L Sharpe; Michael J Beckstead; Ana J Chucair-Elliott; Sarah R Ocañas; Willard M Freeman

doi:10.1016/j.isci.2023.108413

Specificity and efficiency of tamoxifen-mediated Cre induction is equivalent regardless of age

iScience. 2023 Nov 9;26(12):108413. doi: 10.1016/j.isci.2023.108413. eCollection 2023 Dec 15.

Authors

Collyn M Kellogg^{1

2}, Kevin Pham¹, Sunghwan Ko^{1

3}, Jillian E J Cox^{1

3}, Adeline H Machalinski¹, Michael B Stout⁴, Amanda L Sharpe^{5

3}, Michael J Beckstead^{4

6}, Ana J Chucair-Elliott¹, Sarah R Ocañas^{1

3

7}, Willard M Freeman^{1

2

6

3}

Affiliations

¹ Genes & Human Disease Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA.
² Department of Biochemistry & Molecular Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
³ Neuroscience Graduate Program, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
⁴ Aging & Metabolism Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA.
⁵ Department of Pharmaceutical Sciences, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
⁶ Oklahoma City Veterans Affairs Medical Center, Oklahoma City, OK, USA.
⁷ Department of Physiology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.

Abstract

Temporally controlling Cre recombination through tamoxifen (Tam) induction has many advantages for biomedical research. Most studies report early post-natal/juvenile (<2 m.o.) Tam induction, but age-related neurodegeneration and aging studies can require Cre induction in older mice (>12 m.o.). While anecdotally reported as problematic, there are no published comparisons of Tam-mediated Cre induction at early and late ages. Here, microglial-specific Cx3cr1^creERT2 mice were crossed to a floxed NuTRAP reporter to compare Cre induction at early (3-6 m.o.) and late (20 m.o.) ages. Specificity and efficiency of microglial labeling at 21-22 m.o. were identical in mice induced with Tam at early and late ages. Age-related microglial translatomic changes were also similar regardless of Tam induction age. Each Cre and flox mouse line should be independently validated, however, these findings demonstrate that Tam-mediated Cre induction can be performed even into older mouse ages and should be generalizable to other inducible Cre models.

Keywords: Biological sciences; Biological sciences research methodologies; Biology experimental methods; Genomics; Natural sciences.

Abstract

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