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Basement membrane and blood–brain barrier

Lingling Xu, Abhijit Nirwane, Yao Yao
DOI: 10.1136/svn-2018-000198 Published 4 July 2019
Lingling Xu
Department of Pharmaceutical and Biomedical Sciences, University of Georgia, Athens, Georgia, USA
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Abhijit Nirwane
Department of Pharmaceutical and Biomedical Sciences, University of Georgia, Athens, Georgia, USA
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Yao Yao
Department of Pharmaceutical and Biomedical Sciences, University of Georgia, Athens, Georgia, USA
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    Figure 1

    Schematic illustration of the blood–brain barrier. BM, basement membrane.

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    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.

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Vol 4 Issue 2 Table of Contents
Stroke and Vascular Neurology: 4 (2)
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Basement membrane and blood–brain barrier
Lingling Xu, Abhijit Nirwane, Yao Yao
Stroke and Vascular Neurology Jun 2019, 4 (2) 78-82; DOI: 10.1136/svn-2018-000198

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Basement membrane and blood–brain barrier
Lingling Xu, Abhijit Nirwane, Yao Yao
Stroke and Vascular Neurology Jun 2019, 4 (2) 78-82; DOI: 10.1136/svn-2018-000198
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Basement membrane and blood–brain barrier
Lingling Xu, Abhijit Nirwane, Yao Yao
Stroke and Vascular Neurology Jun 2019, 4 (2) 78-82; DOI: 10.1136/svn-2018-000198
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