Journal article
The genetic control of early traits in rat EAE
Journal of neurovirology, Vol.12, pp.16-16
01 May 2006
Abstract
The genetic control of EAE and MS is multigenic, and more than 20 quantitative trait loci (QTL) are likely to regulate the severity and susceptibility of EAE in inbred mice. Each of the identified QTL likely represents a natural allele of a gene with a small overall effect on the disease. For gene identification, it would help to know what that individual gene effect is, and when in the course of the disease induction and manifestation it is likely to act. This level of understanding is missing in MS and EAE research, and, given that EAE must be induced in most rodent models, no current study explains the very first aberrant immune responses that characterize resistance vs. susceptibility. Especially valuable in this regard would be the description of the genetic basis for the loss of immune tolerance to self, as this may have homology to a similar situation in human disease. It should be possible to construct a pathway of early gene activity leading eventually to EAE, and by extension, to MS. The studies in this report are designed to link results from ongoing mapping experiments to the observed component phenotypes of the EAE process that show important differences between the EAE-S and EAE-R inbred strains at very early time points after immunization and EAE induction. LEW EAE-susceptible rats display very polarized responses as early as two days post-immunization, unlike the MHC-identical LER EAE-resistant inbred strain. This early phenotype is likely to be controlled by fewer genetic loci responsible for its manifestation, whereas the genetic architecture underlying the cascade of deleterious events that follows this early distinction is likely to be much more complex. We have investigated the phenotype of early immune responses in the genetically susceptible LEW rat by studying the relevant biomarkers of immune activation in LEW, LER, and LER.chr4 congenic rats induced for EAE with MBP in a minimal adjuvant, CpG. We have also determined the genetic control of the early polarization by mapping the early immune response in LER x LEW F2 intercross rats, and elucidate the mechanism by which this difference occurs. An effort will be made to link the loci for the early immune response polarization and the clinical EAE loci.
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Details
- Title
- The genetic control of early traits in rat EAE
- Creators
- L CortE Blankenhorn
- Publication Details
- Journal of neurovirology, Vol.12, pp.16-16
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Microbiology and Immunology
- Identifiers
- 991019170329104721