Glial dystrophin-associated proteins, laminin and agrin, are downregulated in the brain of mdx mouse

Beatrice Nico, Roberto Tamma, Tiziana Annese, Domenica Mangieri, Annamaria De Luca, Patrizia Corsi, Vincenzo Benagiano, Vito Longo, Enrico Crivellato, Andrea Salmaggi, Domenico Ribatti

Research output: Contribution to journalArticle

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 languageEnglish
Pages (from-to)1645-1660
Number of pages16
JournalLaboratory Investigation
Volume90
Issue number11
DOIs
Publication statusPublished - Nov 2010

Fingerprint

Dystrophin-Associated Proteins
Agrin
Inbred mdx Mouse
Laminin
Basement Membrane
Neuroglia
Dystroglycans
Down-Regulation
Dystrophin
Aquaporin 4
Brain
Confocal Microscopy
Protein Isoforms
Aquaporins
Immunoblotting
Fluorescent Antibody Technique
Electron Microscopy
Immunohistochemistry
Polymerase Chain Reaction
Messenger RNA

Keywords

  • astrocyte
  • basement membrane
  • blood-brain barrier
  • DAPs
  • dystrophy

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Cell Biology
  • Molecular Biology

Cite this

Nico, B., Tamma, R., Annese, T., Mangieri, D., De Luca, A., Corsi, P., ... Ribatti, D. (2010). Glial dystrophin-associated proteins, laminin and agrin, are downregulated in the brain of mdx mouse. Laboratory Investigation, 90(11), 1645-1660. https://doi.org/10.1038/labinvest.2010.149

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 journalArticle

Nico, B, Tamma, R, Annese, T, Mangieri, D, De Luca, A, Corsi, P, Benagiano, V, Longo, V, Crivellato, E, Salmaggi, A & Ribatti, D 2010, 'Glial dystrophin-associated proteins, laminin and agrin, are downregulated in the brain of mdx mouse', Laboratory Investigation, vol. 90, no. 11, pp. 1645-1660. https://doi.org/10.1038/labinvest.2010.149
Nico, Beatrice ; Tamma, Roberto ; Annese, Tiziana ; Mangieri, Domenica ; De Luca, Annamaria ; Corsi, Patrizia ; Benagiano, Vincenzo ; Longo, Vito ; Crivellato, Enrico ; Salmaggi, Andrea ; Ribatti, Domenico. / Glial dystrophin-associated proteins, laminin and agrin, are downregulated in the brain of mdx mouse. In: Laboratory Investigation. 2010 ; Vol. 90, No. 11. pp. 1645-1660.
@article{28798be2adcd4d1ea456a274b803c964,
title = "Glial dystrophin-associated proteins, laminin and agrin, are downregulated in the brain of mdx mouse",
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.",
keywords = "astrocyte, basement membrane, blood-brain barrier, DAPs, dystrophy",
author = "Beatrice Nico and Roberto Tamma and Tiziana Annese and Domenica Mangieri and {De Luca}, Annamaria and Patrizia Corsi and Vincenzo Benagiano and Vito Longo and Enrico Crivellato and Andrea Salmaggi and Domenico Ribatti",
year = "2010",
month = "11",
doi = "10.1038/labinvest.2010.149",
language = "English",
volume = "90",
pages = "1645--1660",
journal = "Laboratory Investigation",
issn = "0023-6837",
publisher = "Nature Publishing Group",
number = "11",

}

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 -