Contributions
Abstract: P436
Type: Poster
Abstract Category: Pathology and pathogenesis of MS - 13 Experimental models
Background and Objectives: The TCR1640 transgenic mice carry a T cell receptor (TCR) specific for myelin oligodendrocyte glycoprotein (MOG) peptide 92-106 and develop spontaneous experimental autoimmune encephalomyelitis (EAE). The disease is more prevalent in female mice and most of them develop an EAE with a relapsing-remitting (RR) disease course whereas the majority of the males present a primary progressive (PP)-EAE. Our objective is to use this model to study different MS disease courses and distinct disease phases and to assess disease-related gender differences.
Methodology and Results: The blood-brain barrier (BBB) permeability and integrity of central nervous (CNS) tissues from TCR1640 mice at different phases in their disease (pre-symptomatic, acute relapse, remission, primary progressive chronic phase), based on their clinical score, was investigated using immunohistochemistry and in vivo tracer. A downregulation of adhesion and junctional molecules, together with increase in leakage (ZO-1, JAM-A, laminin and fibrinogen) in active phases of the disease, accompanied with CD4+ T cell infiltration that remains through remission phase was found. Moreover, intravenously (IV) injected fluorescent-labeled dextran particles indicated that the BBB permeability differs in the various disease stages.
To investigate disease related gender differences observed in these mice adoptive transfer experiments were performed. Immune cells from TCR1640 were injected IV in wildtype SJL/J mice in different combination of genders. Preliminary results shows that the disease course seems to be driven by the gender of the recipients that is: male recipients develop PP disease independently of the gender of the immune cell injected, whereas female recipients develop a RR passive EAE.
Conclusion: The BBB integrity and permeability is affected during the course of EAE in the spontaneous TCR1640 mice, emphasizing the relevance of this model in the study of MS. Moreover, the study of gender difference in this model seems to show that the gender of the recipient dictates the disease course inflicted by the injected cell.
Disclosure: This project is funded by the CIHR.
All the other authors have nothing to disclose for this project.
Abstract: P436
Type: Poster
Abstract Category: Pathology and pathogenesis of MS - 13 Experimental models
Background and Objectives: The TCR1640 transgenic mice carry a T cell receptor (TCR) specific for myelin oligodendrocyte glycoprotein (MOG) peptide 92-106 and develop spontaneous experimental autoimmune encephalomyelitis (EAE). The disease is more prevalent in female mice and most of them develop an EAE with a relapsing-remitting (RR) disease course whereas the majority of the males present a primary progressive (PP)-EAE. Our objective is to use this model to study different MS disease courses and distinct disease phases and to assess disease-related gender differences.
Methodology and Results: The blood-brain barrier (BBB) permeability and integrity of central nervous (CNS) tissues from TCR1640 mice at different phases in their disease (pre-symptomatic, acute relapse, remission, primary progressive chronic phase), based on their clinical score, was investigated using immunohistochemistry and in vivo tracer. A downregulation of adhesion and junctional molecules, together with increase in leakage (ZO-1, JAM-A, laminin and fibrinogen) in active phases of the disease, accompanied with CD4+ T cell infiltration that remains through remission phase was found. Moreover, intravenously (IV) injected fluorescent-labeled dextran particles indicated that the BBB permeability differs in the various disease stages.
To investigate disease related gender differences observed in these mice adoptive transfer experiments were performed. Immune cells from TCR1640 were injected IV in wildtype SJL/J mice in different combination of genders. Preliminary results shows that the disease course seems to be driven by the gender of the recipients that is: male recipients develop PP disease independently of the gender of the immune cell injected, whereas female recipients develop a RR passive EAE.
Conclusion: The BBB integrity and permeability is affected during the course of EAE in the spontaneous TCR1640 mice, emphasizing the relevance of this model in the study of MS. Moreover, the study of gender difference in this model seems to show that the gender of the recipient dictates the disease course inflicted by the injected cell.
Disclosure: This project is funded by the CIHR.
All the other authors have nothing to disclose for this project.