Abstract
In this study, we investigated the involvement of dystrophin-associated proteins (DAPs) and their relationship with the perivascular basement membrane in the brains of mdx mice and controls at the age of 2 months. We analyzed (1) the expression of glial DAPs α-Β-dystroglycan (DG), α-syntrophin, aquaporin-4 (AQP4) water channel, Kir 4.1 and dystrophin isoform (Dp71) by immunocytochemistry, laser confocal microscopy, immunogold electron microscopy, immunoblotting and RT-PCR; (2) the ultrastructure of the basement membrane and expression of laminin and agrin; and (3) the dual immunofluorescence colocalization of AQP4/α-Β-DG, and of Kir 4.1/agrin. The following results were observed in mdx brain as compared with controls: (1) a significant reduction in protein content and mRNA expression of DAPs; (2) ultrastructurally, a thickened and discontinuous appearance of the basement membrane and a significant reduction in laminin and agrin; and (3) a molecular rearrangment of α-Β-DG, coupled with a parallel loss of agrin and Kir 4.1 on basement membrane and glial endfeet. These data indicate that in mdx brain the deficiency in dystrophin and dystrophin isoform (Dp71) is coupled with a reduction of DAP components, coupled with an altered anchoring to the basement membrane.
| Original language | English |
|---|---|
| Pages (from-to) | 1645-1660 |
| Number of pages | 16 |
| Journal | Laboratory Investigation |
| Volume | 90 |
| Issue number | 11 |
| DOIs | |
| Publication status | Published - Nov 2010 |
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Keywords
- astrocyte
- basement membrane
- blood-brain barrier
- DAPs
- dystrophy
ASJC Scopus subject areas
- Pathology and Forensic Medicine
- Cell Biology
- Molecular Biology
Cite this
Glial dystrophin-associated proteins, laminin and agrin, are downregulated in the brain of mdx mouse. / Nico, Beatrice; Tamma, Roberto; Annese, Tiziana; Mangieri, Domenica; De Luca, Annamaria; Corsi, Patrizia; Benagiano, Vincenzo; Longo, Vito; Crivellato, Enrico; Salmaggi, Andrea; Ribatti, Domenico.
In: Laboratory Investigation, Vol. 90, No. 11, 11.2010, p. 1645-1660.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Glial dystrophin-associated proteins, laminin and agrin, are downregulated in the brain of mdx mouse
AU - Nico, Beatrice
AU - Tamma, Roberto
AU - Annese, Tiziana
AU - Mangieri, Domenica
AU - De Luca, Annamaria
AU - Corsi, Patrizia
AU - Benagiano, Vincenzo
AU - Longo, Vito
AU - Crivellato, Enrico
AU - Salmaggi, Andrea
AU - Ribatti, Domenico
PY - 2010/11
Y1 - 2010/11
N2 - In this study, we investigated the involvement of dystrophin-associated proteins (DAPs) and their relationship with the perivascular basement membrane in the brains of mdx mice and controls at the age of 2 months. We analyzed (1) the expression of glial DAPs α-Β-dystroglycan (DG), α-syntrophin, aquaporin-4 (AQP4) water channel, Kir 4.1 and dystrophin isoform (Dp71) by immunocytochemistry, laser confocal microscopy, immunogold electron microscopy, immunoblotting and RT-PCR; (2) the ultrastructure of the basement membrane and expression of laminin and agrin; and (3) the dual immunofluorescence colocalization of AQP4/α-Β-DG, and of Kir 4.1/agrin. The following results were observed in mdx brain as compared with controls: (1) a significant reduction in protein content and mRNA expression of DAPs; (2) ultrastructurally, a thickened and discontinuous appearance of the basement membrane and a significant reduction in laminin and agrin; and (3) a molecular rearrangment of α-Β-DG, coupled with a parallel loss of agrin and Kir 4.1 on basement membrane and glial endfeet. These data indicate that in mdx brain the deficiency in dystrophin and dystrophin isoform (Dp71) is coupled with a reduction of DAP components, coupled with an altered anchoring to the basement membrane.
AB - In this study, we investigated the involvement of dystrophin-associated proteins (DAPs) and their relationship with the perivascular basement membrane in the brains of mdx mice and controls at the age of 2 months. We analyzed (1) the expression of glial DAPs α-Β-dystroglycan (DG), α-syntrophin, aquaporin-4 (AQP4) water channel, Kir 4.1 and dystrophin isoform (Dp71) by immunocytochemistry, laser confocal microscopy, immunogold electron microscopy, immunoblotting and RT-PCR; (2) the ultrastructure of the basement membrane and expression of laminin and agrin; and (3) the dual immunofluorescence colocalization of AQP4/α-Β-DG, and of Kir 4.1/agrin. The following results were observed in mdx brain as compared with controls: (1) a significant reduction in protein content and mRNA expression of DAPs; (2) ultrastructurally, a thickened and discontinuous appearance of the basement membrane and a significant reduction in laminin and agrin; and (3) a molecular rearrangment of α-Β-DG, coupled with a parallel loss of agrin and Kir 4.1 on basement membrane and glial endfeet. These data indicate that in mdx brain the deficiency in dystrophin and dystrophin isoform (Dp71) is coupled with a reduction of DAP components, coupled with an altered anchoring to the basement membrane.
KW - astrocyte
KW - basement membrane
KW - blood-brain barrier
KW - DAPs
KW - dystrophy
UR - http://www.scopus.com/inward/record.url?scp=78049329001&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=78049329001&partnerID=8YFLogxK
U2 - 10.1038/labinvest.2010.149
DO - 10.1038/labinvest.2010.149
M3 - Article
C2 - 20714324
AN - SCOPUS:78049329001
VL - 90
SP - 1645
EP - 1660
JO - Laboratory Investigation
JF - Laboratory Investigation
SN - 0023-6837
IS - 11
ER -