Table 1

Loss-of-function studies on major BM components

Genes	Knockout/mutation	Cre promoter	Knockout phenotype	References
Collagen IV
Collagen 4A1/2	Global knockout	–	BM structural deficiencies and embryonic lethality (E10.5–E11.5)	39
Collagen 4A1	Lacking exon 41 in both alleles	–	Embryonic lethality	45
Collagen 4A1	Lacking exon 41 in one allele	–	Intracerebral haemorrhage and porencephaly	40 41
Collagen 4A1	Conditional knockout	Rosa26-CreER, Tie2-Cre, Pdgfrb-Cre, Gfap-Cre	Intracerebral haemorrhage and porencephaly with different severity	42
Collagen 4A1/2	Missense mutations	–	Vascular defects and brain malformations	43 44
Collagen 4A2	Missense mutations	–	Intracerebral haemorrhage	45
Laminin
Laminin α2	Global knockout	–	BBB disruption	58
Laminin α4	Global knockout	–	Haemorrhage during embryonic/neonatal stage	68
Laminin α5	Global knockout	–	Embryonic lethality (~E17) and defects in neural tube closure and neural crest cell migration	52–54
Laminin α5	Conditional knockout	Tie2-Cre (endothelium)	No gross CNS abnormalities under homeostatic conditions	70 71
Laminin β1	Global knockout	–	Embryonic lethality (E5.5–E6.5)	55
Laminin γ1	Global knockout	–	Embryonic lethality (E5.5–E6.5)	55–57
	Conditional knockout	Nestin-Cre (neural progenitors)	BBB breakdown and intracerebral haemorrhage	1 87
	Conditional knockout	Pdgrfb-Cre (mural cells)	Hydrocephalus and BBB breakdown	51
Nidogen
Nidogen-1	Global knockout	–	Mild BM alteration in brain capillaries	72–74
Nidogen-2	Global knockout	–	No effect on BM formation	75
Nidogen-1 and nidogen-2	Global knockout	–	BM defect and perinatal lethality	77–79
Perlecan
Perlecan	Global knockout	–	Embryonic lethality (E10–E12)	84–86

BBB, blood–brain barrier; BM, basement membrane; CNS, central nervous system.