Table 1.

Loss-of-function studies on major BL components

Targets	Mutations	Cre lines	Phenotypes	References
Collagen 4A1/2	Global KO	-	Embryonic lethality (E10.5-11.5), BM structural deficiencies	[64]
	Missense mutations	-	Vascular defects, brain damage of differing severity	[146–148]
Collagen 4A1	Loss of exon 41 in both alleles	-	Embryonic lethality, ICH	[146]
	Loss of exon 41 in one allele	-	Perinatal lethality with ICH, Porencephaly	[149, 150]
	Conditional knockout	Tie2-Cre	ICH, Increased retinal vascular branching, Porencephaly, Macroangiopathy	[151]
		PDGFRβ-Cre	ICH, Increased retinal vascular branching, Porencephaly, Macroangiopathy	[151]
		GFAP-Cre	Very mild ICH, No defects in retinal branching	[151]
Laminin α2	Global knockout	-	BBB disruption	[132, 152]
Laminin α4	Global knockout	-	Disrupted vascular integrity, Hemorrhage at perinatal stage	[153]
Laminin α5	Global knockout	-	Embryonic lethality (~E17)	[154–156]
	Conditional knockout	Tie2-Cre	No gross abnormalities	[157–159]
Laminin β1	Global knockout	-	Embryonic lethality (E5.5-6.5)	[160]
Laminin γ1	Global knockout	-	Embryonic lethality (E5.5-6.5)	[160–162]
	Conditional knockout	Nestin-Cre	BBB breakdown, ICH	[132, 163]
		CamK2a-Cre	No BBB breakdown or ICH	[132, 163]
		PDGFRβ-Cre	BBB breakdown and hydrocephalus in C57Bl6/FVB mixed background	[134]
			Age-dependent mild BBB breakdown without hydrocephalus in C57Bl6 dominant background	[133]
		SM22α-Cre	No gross abnormalities	[134, 164]
Nidogen 1	Global knockout	-	Grossly normal, Upregulation of nidogen 2	[165–169]
Nidogen 2	Global knockout	-	Grossly normal	[170]
Nidogen 1/2	Global knockout	-	Perinatal lethality, BM defects	[65, 171, 172]
Agrin	Global knockout	-	Embryonic lethality	[173]
	Conditional knockout	Tie2-Cre	Intact BBB structure, Reduced AQP4 expression	[131]
Perlecan	Global knockout	-	Embryonic lethality (E10-12), Developmental defects, BM deterioration in areas with high mechanical stress	[174–176]
	Hypomorph (C1532Yneo)	-	Reduced perlecan secretion, skeletal phenotype similar to Schwartz-Jampel syndrome	[177]
	C1532Y		Normal perlecan secretion, grossly normal	[177]
	Knockout rescued	-	Viable and intact BBB under homeostatic conditions, exacerbated BBB damage and attenuated pericyte accumulation after ischemic stroke	[178]