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Updated: Oct 11, 2025
Renal Ischaemia Reperfusion Injury: A Mouse Model of Injury and Regeneration
Published on: June 7, 2014
Spiny mice activate unique transcriptional programs after severe kidney injury regenerating organ function without
Daryl M Okamura1,2, Chris M Brewer3,2, Paul Wakenight4
1Department of Pediatrics, University of Washington, Seattle, WA 98195, USA.
Abstract:
Fibrosis-driven solid organ failure is an enormous burden on global health. Spiny mice (Acomys) are terrestrial mammals that can regenerate severe skin wounds without scars to avoid predation. Whether spiny mice also regenerate internal organ injuries is unknown. Here, we show that despite equivalent acute obstructive or ischemic kidney injury, spiny mice fully regenerate nephron structure and organ function without fibrosis, whereas C57Bl/6 or CD1 mice progress to complete organ failure with extensive renal fibrosis. Two mechanisms for vertebrate regeneration have been proposed that emphasize either extrinsic (pro-regenerative macrophages) or intrinsic (surviving cells of the organ itself) controls. Comparative transcriptome analysis revealed that the Acomys genome appears poised at the time of injury to initiate regeneration by surviving kidney cells, whereas macrophage accumulation was not detected until about day 7. Thus, we provide evidence for rapid activation of a gene expression signature for regenerative wound healing in the spiny mouse kidney.
Insights
Spiny mice (Acomys) can regenerate injured kidneys without scarring, unlike other mice. This suggests intrinsic kidney cell activation drives regeneration, offering insights into organ repair.
Area of Science:
- Regenerative medicine
- Comparative physiology
- Organ fibrosis
Background:
- Fibrosis-driven solid organ failure is a major global health issue.
- Spiny mice (Acomys) exhibit scarless skin wound healing.
- The regenerative capacity of spiny mouse internal organs remains unexplored.
Purpose of the Study:
- To investigate if spiny mice can regenerate internal organ injuries, specifically the kidney.
- To compare kidney regeneration in spiny mice versus conventional mouse models (C57Bl/6, CD1).
- To elucidate the underlying mechanisms of kidney regeneration in Acomys.
Main Methods:
- Induction of acute obstructive or ischemic kidney injury in spiny mice and control mice.
- Assessment of nephron structure and organ function recovery.
- Comparative transcriptome analysis to identify gene expression patterns during regeneration.
Main Results:
- Spiny mice fully regenerated kidney structure and function post-injury without fibrosis.
- Control mice (C57Bl/6, CD1) developed significant renal fibrosis and organ failure.
- Transcriptome analysis indicated early activation of intrinsic regenerative pathways in Acomys kidney cells, preceding macrophage infiltration.
Conclusions:
- Spiny mice possess a remarkable capacity for kidney regeneration, contrasting with fibrotic failure in other mouse strains.
- Regeneration in Acomys appears driven by intrinsic surviving kidney cells, not primarily by extrinsic factors like macrophages.
- This study reveals a unique gene expression signature for regenerative wound healing in the Acomys kidney, offering potential therapeutic targets.
