Table 1.

Summary of phenotypic differences observed between acute and chronic CCM models compared to human

	Acute murine	Chronic murine	Human
Genotype	Cdh5iCreERT2Krit1ECKO	Krit1+/−Msh2−/−	KRIT1+/−
	PdgfbiCreERT2Krit1ECKO	Pdcd10+/−	CCM2+/−
	PdgfbiCreERT2Pdcd10 ECKO	Pdcd10+/−Trp53−/−	PDCD10+/−
Lesion burden and distribution (Figure 1 and 2)	Higher lesion burden than chronic models Localized in the cerebellum More aggressive in Pdcd10 genotype	Lower lesion burden than acute models Random brain volume distribution More aggressive in Pdcd10 genotype	Lesion burden depends on the genotype, greater with PDCD1039 Random brain volume distribution in familial cases; near developmental venous anomalies in sporadic cases 45
ROCK activity in ECs (Figure 3)	Robust in lesional ECs, present in hindbrain normal capillaries	Robust in lesional ECs, present in normal capillaries throughout the brain	Robust in lesional ECs, present in normal brain capillaries in familial cases 39
Lesional non-heme iron deposition * (Figure 4)	Minimal in Stage 2 lesions	Robust in Stage 2 lesions	Robust in CCM lesions 18
Infiltrated inflammatory cells (B and T cells) * (Figure 5)	Minimal in Stage 2 lesions	Robust in Stage 2 lesions	Robust in CCM lesions 23
Tight junctions (Figure 6)	Lower prevalence of lesional ECs expressing occludin compared to normal ECs	Lower prevalence of lesional ECs expressing occludin and ZO-1 compared to normal ECs	Lower expression of claudin-5, occludin and ZO-1 on lesional ECs compared to normal ECs 50

Abbreviations: CCM, cerebral cavernous malformation; ECs, endothelial cells; ZO-1, zona occludens-1

^*relative to lesional area