Table 1 Loss-of-function studies on major BL components

Collagen 4A1/2

Global KO

-

Embryonic lethality (E10.5-11.5), BM structural deficiencies

[64]

Missense mutations

-

Vascular defects, brain damage of differing severity

[146,147,148]

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)

[154,155,156]

Conditional knockout

Tie2-Cre

No gross abnormalities

[157,158,159]

Laminin β1

Global knockout

-

Embryonic lethality (E5.5-6.5)

[160]

Laminin γ1

Global knockout

-

Embryonic lethality (E5.5-6.5)

[160,161,162]

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

[165,166,167,168,169]

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

[174,175,176]

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]