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<p>Small molecules such as PLX5622 for microglia depletion and tamoxifen for inducible Cre recombination are commonly used in mouse research. Traditional application methods such as drug-infused chow, oral gavage or injections have limitations, including uncontrolled dosing (chow) or risk of injury and/or stress (gavage or injections). Here, to address these issues, we have developed an alternative oral drug delivery system using a gel-based rodent maintenance diet that allows for controlled consumption and adjustment of dosage and is suitable for water-insoluble small molecules. We tested DietGel 93M (93M) infused with PLX5622 (0.8 mg/g and 2.0 mg/g) in the <i>Cx3cr1</i><sup><i>gfp/+</i></sup> retinal microglia reporter mouse and tamoxifen-infused 93M (0.3125 mg/g) in the Rlbp1-CreERT2<i>;Rosa</i><sup><i>ai14</i></sup> mouse with an inducible tdTomato reporter in retinal Müller glia. Mice were single caged and received daily batches of PLX5622-infused 93M over 14 days or tamoxifen-infused 93M for 1 or 3 days followed by a 14-day observation period. Longitudinal scanning laser ophthalmoscopy in vivo and fixed-tissue imaging were used to track GFP and tdTomato expression. Following evaluation of a suitable 93M consumption rate to sustain body weight, the PLX5622-93M diet at both concentrations tested showed a 94% microglia depletion rate at 3 days and &gt;99% after 1 and 2 weeks. The tamoxifen-93M diet confirmed suitability for inducible Cre recombination, with significant treatment time-dependent efficacy and a positive correlation between total tamoxifen dose and tdTomato expression. This study demonstrates that a diet gel-based drug delivery system offers a minimally invasive alternative to current drug application methods for PLX5622 and tamoxifen. This approach could be useful for other drugs or tissues beyond the retina.</p>

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Diet gel-based oral drug delivery system for controlled dosing of small molecules for microglia depletion and inducible Cre recombination in mice

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年9月26日

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  • Joel Jovanovic,
  • Megan L. Stone,
  • Samantha R. Dooyema,
  • Yuankai K. Tao,
  • Sabine Fuhrmann,
  • Edward M. Levine

摘要

Small molecules such as PLX5622 for microglia depletion and tamoxifen for inducible Cre recombination are commonly used in mouse research. Traditional application methods such as drug-infused chow, oral gavage or injections have limitations, including uncontrolled dosing (chow) or risk of injury and/or stress (gavage or injections). Here, to address these issues, we have developed an alternative oral drug delivery system using a gel-based rodent maintenance diet that allows for controlled consumption and adjustment of dosage and is suitable for water-insoluble small molecules. We tested DietGel 93M (93M) infused with PLX5622 (0.8 mg/g and 2.0 mg/g) in the Cx3cr1gfp/+ retinal microglia reporter mouse and tamoxifen-infused 93M (0.3125 mg/g) in the Rlbp1-CreERT2;Rosaai14 mouse with an inducible tdTomato reporter in retinal Müller glia. Mice were single caged and received daily batches of PLX5622-infused 93M over 14 days or tamoxifen-infused 93M for 1 or 3 days followed by a 14-day observation period. Longitudinal scanning laser ophthalmoscopy in vivo and fixed-tissue imaging were used to track GFP and tdTomato expression. Following evaluation of a suitable 93M consumption rate to sustain body weight, the PLX5622-93M diet at both concentrations tested showed a 94% microglia depletion rate at 3 days and >99% after 1 and 2 weeks. The tamoxifen-93M diet confirmed suitability for inducible Cre recombination, with significant treatment time-dependent efficacy and a positive correlation between total tamoxifen dose and tdTomato expression. This study demonstrates that a diet gel-based drug delivery system offers a minimally invasive alternative to current drug application methods for PLX5622 and tamoxifen. This approach could be useful for other drugs or tissues beyond the retina.