Animal Models in Studying Cerebral Arteriovenous Malformation

Table 2

The highlights of AVM models by gene manipulation.

Type	Author [Reference]	Year	Animal	Characteristics	Applications
AVM lesions by gene manipulation	Bourdeau et al. [19]; Satomi et al. [20]	1999; 2003	mouse	Generating Eng mutant mice: modest cerebrovascular abnormality	To investigate the pathogenic mechanisms of AVMs in genetic factors
	Oh et al. [21]; Srinivasan et al. [22]	2000; 2003	mouse	Generating Alk1 mutant mice: minimal cerebrovascular abnormality
	Xu et al. [23]	2004	mouse	Focal virus-mediated VEGF gene transferred in the brain of Eng mice: cerebral microvascular dysplasia	To investigate the pathogenic mechanisms of AVMs in genetic and environmental factors
	Hao et al. [24, 25]	2008	mouse	Focal virus-mediated VEGF gene transferred in the brain of Alk1 mice: cerebral microvascular dysplasia, less severe compared to Eng mice, promoted by increased cerebral perfusion
	Sung et al. [26]	2009	mouse	Conditional knockout of Alk1 by globally expressed Cre in adult mice: AV fistula formations and spontaneous hemorrhage in other organs, not remarkable in the brain	To investigate the pathogenic and hemorrhagic mechanisms of AVMs
	Choi et al. [27]	2014	mouse	Conditional knockout of Eng by globally expressed Cre in adult mice: no remarkable effects on brain vasculature, angiogenesis and cerebrovascular lesions mimicking human AVM nidus developed with focal virus-mediated VEGF gene transferred
	Walker et al. [28]	2011	mouse	Focal virus-mediated Cre and VEGF gene transferred in Alk1 mice: AVM lesions resembling the human disease	To investigate the pathogenic mechanisms of AVMs and to test the potential treatments
	Choi et al. [29]	2012	mouse	Focal virus-mediated Cre and VEGF gene transferred in Eng mice: AVM lesions resembling the human disease
	Chen et al. [30]	2014	mouse	Conditional knockout of Alk1 specifically in endothelial cells in adult mice: AVM formation and spontaneous hemorrhage in other organs and brain areas with previously focal virus-mediated VEGF gene transferred	To evaluated the role of endothelia in the pathogenesis of AVMs
	Mahmoud et al. [31]	2010	mouse	Conditional knockout of Eng specifically in endothelial cells in postnatal mice: endothelial proliferation and AVM formation in neonatal retina, local venomegaly in adult skin induced by angiogenic stimulation
	Milton et al. [32]	2012	mouse	Mating Alk1 mice with SM22-Cre mutant mice: spontaneous AVMs in the brain and spinal cord, partial lesions undergoing spontaneous hemorrhage	To investigate the hemorrhagic mechanisms of AVMs and to test the potential treatments
	Choi et al. [27]	2014	mouse	Mating Eng mice with SM22-Cre mutant mice: spontaneous AVMs in the brain and spinal cord, partial lesions undergoing spontaneous hemorrhage
	Murphy et al. [33]	2008	mouse	Induced overexpression of constitutively active Notch4 and Notch1 in neonatal mice: hallmarks of AVMs in the brain and cerebral hemorrhage	To investigate the pathogenic mechanisms of AVMs in genetic factors
	Yao et al. [34]	2013	mouse	Generating Mgp mutant mice: vascular enlargement and AV shunting
	Nielsen et al. [35]	2014	mouse	Deleting Rbpj gene in neonatal mice: AV shunting and tortuous vessels

AVM: arteriovenous malformation; VEGF: vascular endothelial growth factor.