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Updated: Sep 20, 2025
Induction and Micro-CT Imaging of Cerebral Cavernous Malformations in Mouse Model
Published on: September 4, 2017
Cerebral cavernous malformation development in chronic mouse models driven by dual recombinases induced gene deletion
Xi Yang1, Zifeng Dai2, Caixia Gao3
1Department of Pharmacology and Tianjin Key Laboratory of Inflammation Biology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China.
Abstract:
Cerebral cavernous malformation (CCM) is a brain vascular disease which can cause stroke, cerebral hemorrhage and neurological deficits in affected individuals. Loss-of-function mutations in three genes (CCM1, CCM2 and CCM3) cause CCM disease. Multiple mouse models for CCM disease have been developed although each of them are associated with various limitations. Here, we employed the Dre-Cre dual recombinase system to specifically delete Ccm genes in brain endothelial cells. In this new series of CCM mouse models, robust CCM lesions now develop in the cerebrum. The survival curve and lesion burden analysis revealed that Ccm2 deletion causes modest CCM lesions with a median life expectance of ∼10 months and Ccm3 gene deletion leads to the most severe CCM lesions with median life expectance of ∼2 months. The extended lifespan of these mutant mice enables their utility in behavioral analyses of neurologic deficits in adult mice, and allow the development of methods to quantify lesion burden in mice over time and also permit longitudinal drug testing in live animals.
Insights
New mouse models for cerebral cavernous malformation (CCM) were created by deleting CCM genes in brain cells. These models enable further study of this vascular disease and potential treatments.
Area of Science:
- Neuroscience
- Genetics
- Vascular Biology
Background:
- Cerebral cavernous malformation (CCM) is a debilitating brain vascular disease.
- CCM causes stroke, hemorrhage, and neurological deficits.
- Existing mouse models have limitations for studying CCM.
Purpose of the Study:
- To develop novel mouse models for CCM by targeting CCM genes in brain endothelial cells.
- To characterize the severity and progression of CCM lesions in these new models.
- To establish tools for studying CCM-related neurological deficits and testing therapies.
Main Methods:
- Utilized the Dre-Cre dual recombinase system for targeted gene deletion.
- Generated mouse models with specific loss-of-function mutations in Ccm1, Ccm2, or Ccm3 genes.
- Analyzed CCM lesion development, survival rates, and lesion burden.
Main Results:
- Robust CCM lesions developed in the cerebrum of the new mouse models.
- Ccm2 deletion resulted in modest CCM lesions and a median lifespan of ~10 months.
- Ccm3 deletion caused severe CCM lesions with a median lifespan of ~2 months.
Conclusions:
- The developed mouse models accurately recapitulate CCM disease.
- These models offer extended lifespans for studying neurological deficits and drug efficacy.
- This research provides valuable tools for advancing CCM disease research and therapeutic development.
