Table 1

Loss-of-function studies on major BM components

GenesKnockout/mutationCre promoterKnockout phenotypeReferences
Collagen IV
 Collagen 4A1/2Global knockout–BM structural deficiencies and embryonic lethality (E10.5–E11.5) 39
 Collagen 4A1Lacking exon 41 in both alleles–Embryonic lethality 45
 Collagen 4A1Lacking exon 41 in one allele–Intracerebral haemorrhage and porencephaly 40 41
 Collagen 4A1Conditional knockoutRosa26-CreER, Tie2-Cre, Pdgfrb-Cre, Gfap-CreIntracerebral haemorrhage and porencephaly with different severity 42
 Collagen 4A1/2Missense mutations–Vascular defects and brain malformations 43 44
 Collagen 4A2Missense mutations–Intracerebral haemorrhage 45
Laminin
 Laminin α2Global knockout–BBB disruption 58
 Laminin α4Global knockout–Haemorrhage during embryonic/neonatal stage 68
 Laminin α5Global knockout–Embryonic lethality (~E17) and defects in neural tube closure and neural crest cell migration 52–54
Conditional knockoutTie2-Cre
(endothelium)		No gross CNS abnormalities under homeostatic conditions 70 71
 Laminin β1Global knockout–Embryonic lethality (E5.5–E6.5) 55
 Laminin γ1Global knockout–Embryonic lethality (E5.5–E6.5) 55–57
Conditional knockoutNestin-Cre (neural progenitors)BBB breakdown and intracerebral haemorrhage 1 87
Conditional knockoutPdgrfb-Cre (mural cells)Hydrocephalus and BBB breakdown 51
Nidogen
 Nidogen-1Global knockout–Mild BM alteration in brain capillaries 72–74
 Nidogen-2Global knockout–No effect on BM formation 75
 Nidogen-1 and nidogen-2Global knockout–BM defect and perinatal lethality 77–79
Perlecan
 PerlecanGlobal knockout–Embryonic lethality (E10–E12) 84–86

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