Advanced

The axon reaction : identifying the genes that make a difference

Piehl, Fredrik; Swanberg, Maria LU and Lidman, Olle (2007) In Physiology and Behavior 92(1-2). p.67-74
Abstract

Numerous CNS diseases of primarily non-inflammatory origin, such as idiopathic neurodegenerative diseases, contain elements of inflammation, with T cell infiltration, MHC class II expression and neuron/axon damage. Gene mapping in human clinical materials have in most cases failed to unravel discrete genes, since most genes instrumental in non-Mendelian forms of these complex diseases are likely to modestly affect risk, be evolutionary conserved in the population and vary between individuals. We here describe the exploration of susceptibility to neurodegeneration and inflammatory glial activation in response to mechanical nerve injury using experimental genetic models. The response to ventral root avulsion, which is a simple and... (More)

Numerous CNS diseases of primarily non-inflammatory origin, such as idiopathic neurodegenerative diseases, contain elements of inflammation, with T cell infiltration, MHC class II expression and neuron/axon damage. Gene mapping in human clinical materials have in most cases failed to unravel discrete genes, since most genes instrumental in non-Mendelian forms of these complex diseases are likely to modestly affect risk, be evolutionary conserved in the population and vary between individuals. We here describe the exploration of susceptibility to neurodegeneration and inflammatory glial activation in response to mechanical nerve injury using experimental genetic models. The response to ventral root avulsion, which is a simple and reproducible model of nerve injury-induced neurodegeneration and inflammation, was examined in a panel of inbred rat strains. A whole genome scan subsequently performed in a F2(DAxPVG) intercross identified quantitative trait loci (QTLs) regulating different features of the nerve injury response. Fine mapping in an advanced intercross line revealed polymorphisms in the Mhc2ta gene as being responsible for strain differences in MHC class II expression. Furthermore, a polymorphism in the syntenic human gene, MHC2TA, was associated both with lower expression of MHC class II-associated genes and increased susceptibility to inflammatory diseases. These results provide important insights into the genetic regulation of fundamental physiological responses of the nervous system to damage and demonstrate relevance also for human diseases.

(Less)
Please use this url to cite or link to this publication:
author
publishing date
type
Contribution to journal
publication status
published
keywords
Animals, Axons, Crosses, Genetic, Disease Models, Animal, Genes, MHC Class II, Genetic Predisposition to Disease, Male, Neurodegenerative Diseases, Nuclear Proteins, Polymorphism, Genetic, Quantitative Trait Loci, Rats, Rats, Inbred Strains, Species Specificity, Spinal Nerve Roots, Trans-Activators, Comparative Study, Journal Article, Research Support, Non-U.S. Gov't
in
Physiology and Behavior
volume
92
issue
1-2
pages
8 pages
publisher
Elsevier
external identifiers
  • scopus:34548542838
ISSN
0031-9384
DOI
10.1016/j.physbeh.2007.05.030
language
English
LU publication?
no
id
598a4128-5402-4c61-9672-661b3ee88cea
date added to LUP
2017-02-22 09:45:57
date last changed
2017-02-26 04:46:06
@article{598a4128-5402-4c61-9672-661b3ee88cea,
  abstract     = {<p>Numerous CNS diseases of primarily non-inflammatory origin, such as idiopathic neurodegenerative diseases, contain elements of inflammation, with T cell infiltration, MHC class II expression and neuron/axon damage. Gene mapping in human clinical materials have in most cases failed to unravel discrete genes, since most genes instrumental in non-Mendelian forms of these complex diseases are likely to modestly affect risk, be evolutionary conserved in the population and vary between individuals. We here describe the exploration of susceptibility to neurodegeneration and inflammatory glial activation in response to mechanical nerve injury using experimental genetic models. The response to ventral root avulsion, which is a simple and reproducible model of nerve injury-induced neurodegeneration and inflammation, was examined in a panel of inbred rat strains. A whole genome scan subsequently performed in a F2(DAxPVG) intercross identified quantitative trait loci (QTLs) regulating different features of the nerve injury response. Fine mapping in an advanced intercross line revealed polymorphisms in the Mhc2ta gene as being responsible for strain differences in MHC class II expression. Furthermore, a polymorphism in the syntenic human gene, MHC2TA, was associated both with lower expression of MHC class II-associated genes and increased susceptibility to inflammatory diseases. These results provide important insights into the genetic regulation of fundamental physiological responses of the nervous system to damage and demonstrate relevance also for human diseases.</p>},
  author       = {Piehl, Fredrik and Swanberg, Maria and Lidman, Olle},
  issn         = {0031-9384},
  keyword      = {Animals,Axons,Crosses, Genetic,Disease Models, Animal,Genes, MHC Class II,Genetic Predisposition to Disease,Male,Neurodegenerative Diseases,Nuclear Proteins,Polymorphism, Genetic,Quantitative Trait Loci,Rats,Rats, Inbred Strains,Species Specificity,Spinal Nerve Roots,Trans-Activators,Comparative Study,Journal Article,Research Support, Non-U.S. Gov't},
  language     = {eng},
  month        = {09},
  number       = {1-2},
  pages        = {67--74},
  publisher    = {Elsevier},
  series       = {Physiology and Behavior},
  title        = {The axon reaction : identifying the genes that make a difference},
  url          = {http://dx.doi.org/10.1016/j.physbeh.2007.05.030},
  volume       = {92},
  year         = {2007},
}