Advanced

A Role for the Non-Receptor Tyrosine Kinase Abl2/Arg in Experimental Neuroinflammation

Jacobsen, Freja Aksel ; Scherer, Alexander N. ; Mouritsen, Jeppe ; Bragadóttir, Hera ; Thomas Bäckström, B. ; Sardar, Samra ; Holmberg, Dan LU ; Koleske, Anthony J. and Andersson, Åsa LU (2018) In Journal of Neuroimmune Pharmacology 13(2). p.265-276
Abstract

Multiple sclerosis is a neuroinflammatory degenerative disease, caused by activated immune cells infiltrating the CNS. The disease etiology involves both genetic and environmental factors. The mouse genetic locus, Eae27, linked to disease development in the experimental autoimmune encephalomyelitis (EAE) model for multiple sclerosis, was studied in order to identify contributing disease susceptibility factors and potential drug targets for multiple sclerosis. Studies of an Eae27 congenic mouse strain, revealed that genetic variation within Eae27 influences EAE development. The Abl2 gene, encoding the non-receptor tyrosine kinase Arg, is located in the 4,1 megabase pair long Eae27 region. The Arg protein plays an important role in... (More)

Multiple sclerosis is a neuroinflammatory degenerative disease, caused by activated immune cells infiltrating the CNS. The disease etiology involves both genetic and environmental factors. The mouse genetic locus, Eae27, linked to disease development in the experimental autoimmune encephalomyelitis (EAE) model for multiple sclerosis, was studied in order to identify contributing disease susceptibility factors and potential drug targets for multiple sclerosis. Studies of an Eae27 congenic mouse strain, revealed that genetic variation within Eae27 influences EAE development. The Abl2 gene, encoding the non-receptor tyrosine kinase Arg, is located in the 4,1 megabase pair long Eae27 region. The Arg protein plays an important role in cellular regulation and is, in addition, involved in signaling through the B- and T-cell receptors, important for the autoimmune response. The presence of a single nucleotide polymorphism causing an amino acid change in a near actin-interacting domain of Arg, in addition to altered lymphocyte activation in the congenic mice upon immunization with myelin antigen, makes Abl2/Arg a candidate gene for EAE. Here we demonstrate that the non-synonymous SNP does not change Arg’s binding affinity for F-actin but suggest a role for Abl kinases in CNS inflammation pathogenesis by showing that pharmacological inhibition of Abl kinases ameliorates EAE, but not experimental arthritis.

(Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Abl kinase, Arg, Eae27, Experimental autoimmune encephalomyelitis, Imatinib
in
Journal of Neuroimmune Pharmacology
volume
13
issue
2
pages
265 - 276
publisher
Springer
external identifiers
  • pmid:29550892
  • scopus:85044043378
ISSN
1557-1890
DOI
10.1007/s11481-018-9783-8
language
English
LU publication?
yes
id
47f31612-1dee-4d74-8d0c-9b1a18e8ea16
date added to LUP
2018-04-04 14:13:01
date last changed
2020-01-16 03:18:21
@article{47f31612-1dee-4d74-8d0c-9b1a18e8ea16,
  abstract     = {<p>Multiple sclerosis is a neuroinflammatory degenerative disease, caused by activated immune cells infiltrating the CNS. The disease etiology involves both genetic and environmental factors. The mouse genetic locus, Eae27, linked to disease development in the experimental autoimmune encephalomyelitis (EAE) model for multiple sclerosis, was studied in order to identify contributing disease susceptibility factors and potential drug targets for multiple sclerosis. Studies of an Eae27 congenic mouse strain, revealed that genetic variation within Eae27 influences EAE development. The Abl2 gene, encoding the non-receptor tyrosine kinase Arg, is located in the 4,1 megabase pair long Eae27 region. The Arg protein plays an important role in cellular regulation and is, in addition, involved in signaling through the B- and T-cell receptors, important for the autoimmune response. The presence of a single nucleotide polymorphism causing an amino acid change in a near actin-interacting domain of Arg, in addition to altered lymphocyte activation in the congenic mice upon immunization with myelin antigen, makes Abl2/Arg a candidate gene for EAE. Here we demonstrate that the non-synonymous SNP does not change Arg’s binding affinity for F-actin but suggest a role for Abl kinases in CNS inflammation pathogenesis by showing that pharmacological inhibition of Abl kinases ameliorates EAE, but not experimental arthritis.</p>},
  author       = {Jacobsen, Freja Aksel and Scherer, Alexander N. and Mouritsen, Jeppe and Bragadóttir, Hera and Thomas Bäckström, B. and Sardar, Samra and Holmberg, Dan and Koleske, Anthony J. and Andersson, Åsa},
  issn         = {1557-1890},
  language     = {eng},
  number       = {2},
  pages        = {265--276},
  publisher    = {Springer},
  series       = {Journal of Neuroimmune Pharmacology},
  title        = {A Role for the Non-Receptor Tyrosine Kinase Abl2/Arg in Experimental Neuroinflammation},
  url          = {http://dx.doi.org/10.1007/s11481-018-9783-8},
  doi          = {10.1007/s11481-018-9783-8},
  volume       = {13},
  year         = {2018},
}