A Novel Mouse Model Demonstrates In Vivo Replenishment of Central Nervous System Pericytes After Successful Acute Ablation

Atak, D.; Yildiz, E.; Ozkan, E.; Yousefi, M.; Ozkan, A.; Gokyuzu, A. B.; Kizilirmak, A. B.; Alnajjar, I. A.; Kanar, C.; Caan, Z. L.; Zeybek, S. U.; Kucukali, C. I.; Tuzun, E.; Gursoy-Ozdemir, Y.; Vural, A.

doi:10.1101/2024.09.27.614665

bioRxiv · 10.1101/2024.09.27.614665

A Novel Mouse Model Demonstrates In Vivo Replenishment of Central Nervous System Pericytes After Successful Acute Ablation

Atak, D.·Yildiz, E.·Ozkan, E.·Yousefi, M.·Ozkan, A.·Gokyuzu, A. B.·Kizilirmak, A. B.·Alnajjar, I. A.·Kanar, C.·Caan, Z. L.·Zeybek, S. U.·Kucukali, C. I.·Tuzun, E.·Gursoy-Ozdemir, Y.·Vural, A.

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Abstract

Central nervous system (CNS) pericytes play crucial roles in vascular development and blood-brain barrier maturation during prenatal development, as well as in regulating cerebral blood flow in adults. They have also been implicated in the pathogenesis of numerous neurological disorders. However, the behavior of pericytes in the adult brain after injury remains poorly understood, partly due to limitations in existing pericyte ablation models. To investigate pericyte responses following acute ablation, we developed a tamoxifen-inducible pericyte ablation model by crossing PDGFR{beta}-P2A-CreERT2 and Rosa26-DTA176 transgenic mouse lines. Using this model, we studied the effects of different tamoxifen doses and conducted histological examinations 15 and 60 days post-injection to assess both short- and long-term impacts of pericyte ablation. Our results demonstrate that a low dose of tamoxifen effectively ablates CNS pericytes in mice without reducing survival or causing significant systemic side effects, such as weight loss. Additionally, we found that the extent of pericyte depletion varies between the cortex and the spinal cords gray and white matter regions. Importantly, both pericyte coverage and numbers increased in the weeks following acute ablation, indicating the regenerative capacity of CNS pericytes in vivo. This model offers a valuable tool for future studies on the role of pericytes in neurological disorders, overcoming the limitations of constitutive pericyte ablation models.

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Atak, D., Yildiz, E., Ozkan, E., Yousefi, M., Ozkan, A., Gokyuzu, A. B., Kizilirmak, A. B., Alnajjar, I. A., Kanar, C., Caan, Z. L., Zeybek, S. U., Kucukali, C. I., Tuzun, E., Gursoy-Ozdemir, Y., Vural, A.. 2024-09-28. A Novel Mouse Model Demonstrates In Vivo Replenishment of Central Nervous System Pericytes After Successful Acute Ablation. https://doi.org/10.1101/2024.09.27.614665

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