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. 2023 May 25;194(1):53–69. doi: 10.1093/toxsci/kfad049

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© The Author(s) 2023. Published by Oxford University Press on behalf of the Society of Toxicology.

This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (https://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact journals.permissions@oup.com

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Figure 4. — Degradation of CDK2 or CDK5 outside the brain in adult mice only causes a morphological change in the testis of CDK2^dTAG mice. A–C, Potent degradation of CDK2 or CDK5 for 14 days using dTAG-13 delivered in Formulation no. 4 only causes a morphological change in the testis. A, Study outline for treating HOM WT, CDK2^dTAG or CDK5^dTAG mice with dTAG-13 delivered in Formulation no. 4 for 14 days. B, CDK2-specific and injection site histopathology results following 14 days of dTAG-13 treatment using Formulation no. 4. For most findings, H&E slides from 5 to 8 mice were evaluated by a board-certified veterinary anatomic pathologist. Results from male and female mice were combined due to a lack of gender specific differences. Findings deemed secondary to injection site toxicity are displayed in Supplementary Figure 5. C, Levels of CDK2 or CDK5 via a plate-based HiBit assay in HOM CDK2^dTAG or CDK5^dTAG mice after 2 days of dosing dTAG-13 or vehicle in vivo using Formulation no. 4. Data points are from individual mice and are relative to the average HiBit signal from vehicle-treated mice. A dashed line separates results from CDK2^dTAG and CDK5^dTAG mice. For most tissues, results from 2 male and 2 female mice are shown. M, male; F, female. ND, not determined. D–F, Modest degradation of CDK2 or CDK5 for 26 days using dTAG-13 delivered in Formulation no. 1 only causes a morphological change in the testis. D, Study outline for treating HOM CDK2^dTAG or CDK5^dTAG mice with dTAG-13 in Formulation no. 1 for 26 days. E, Summary of all histopathologic findings. For most findings, H&E slides from at least 4 mice per gender were evaluated by a board-certified veterinary anatomic pathologist. Results from male and female mice were combined due to lack of gender differences. Degen, degeneration, regen, regeneration. F, Levels of CDK2 or CDK5 via a plate-based HiBit assay in HOM CDK2^dTAG or CDK5^dTAG mice after 2 days of dosing dTAG-13 or vehicle in vivo using Formulation no. 1. Values are from individual mice and are relative to the average HiBit signal from vehicle treated mice. A dashed line separates results from CDK2^dTAG and CDK5^dTAG mice. For most tissues, results from 1 male and 1 female mouse are shown.