Journal article
Genetic Analysis of the Influence of Neuroantigen-Complete Freund’s Adjuvant Emulsion Structures on the Sexual Dimorphism and Susceptibility to Experimental Allergic Encephalomyelitis
The American journal of pathology, v 163(4), pp 1623-1632
Oct 2003
PMID: 14507669
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
The induction of organ-specific autoimmune diseases, such as experimental allergic encephalomyelitis (EAE) the principal animal model of multiple sclerosis (MS), relies on the use of complete Freund’s adjuvant (CFA) emulsions. In this study we report that the physical structure of the particles comprising neuroantigen-CFA emulsions significantly influences the genetic control of the incidence and sexual dimorphism seen in EAE. Immunization of (B10.S/SgMcdJ × SJL/J) F
2
mice segregating the quantitative trait loci (QTL) controlling EAE in susceptible SJL/J and resistant B10.S/SgMcdJ mice with emulsions consisting of particles where the
Mycobacterium tuberculosis
and neuroantigens are localized on the phase surfaces led to severe EAE in 98.8% of the mice, overriding all sex-specific and non-sex-specific genetic checkpoints. In contrast, F
2
mice immunized with emulsions where the bacterial products and encephalitogens are buried inside the water/oil vesicles exhibited a significant reduction in disease incidence (7.5%) and a sexual dimorphism (5% male
versus
10% female). A genome scan identified QTL on chromosomes 7 and 11 controlling the sexual dimorphism as a function of the physical structure of the emulsion. The chromosome 11 QTL co-localizes with
eae6b
, and with
Il12b
and heptatitis A virus cellular receptor 2 (
Havcr2
, formerly known as
Timd3
), both of which are candidate genes for this QTL. Sequence analysis of the SJL/J and B10.S/SgMcdJ alleles indicates that both gene products are structurally monomorphic. Expression analysis also excluded both as candidates for this sex-specific QTL. These results reinforce the importance of gene-environment interactions in initiating and propagating autoimmune disease of the central nervous system, particularly in the context of susceptibility to MS and disease heterogeneity.
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Details
- Title
- Genetic Analysis of the Influence of Neuroantigen-Complete Freund’s Adjuvant Emulsion Structures on the Sexual Dimorphism and Susceptibility to Experimental Allergic Encephalomyelitis
- Creators
- Parley D Fillmore - From the Department of Veterinary PathobiologyMatthew Brace - From the Department of Veterinary PathobiologyScott A Troutman - From the Department of Veterinary PathobiologyElizabeth P Blankenhorn - From the Department of Veterinary PathobiologySean Diehl - From the Department of Veterinary PathobiologyMercedes Rincon - From the Department of Veterinary PathobiologyCory Teuscher - From the Department of Veterinary Pathobiology
- Publication Details
- The American journal of pathology, v 163(4), pp 1623-1632
- Publisher
- American Society for Investigative Pathology
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- [Retired Faculty]
- Web of Science ID
- WOS:000185517500039
- Scopus ID
- 2-s2.0-0141425572
- Other Identifier
- 991014877902704721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Pathology