Dissection of a locus on mouse chromosome 5 reveals arthritis promoting and inhibitory genes
Open accessAbstract
Introduction: In a cross between two mouse strains, the susceptible B10.RIII (H-2 r) and resistant RIIIS/J (H-2 r) strains, a locus on mouse chromosome 5 (Eae39) was previously shown to control experimental autoimmune encephalomyelitis (EAE). Recently, quantitative trait loci (QTL), linked to disease in different experimental arthritis models, were mapped to this region. The aim of the present study was to investigate whether genes within Eae39, in addition to EAE, control development of collagen-induced arthritis (CIA). Methods: CIA, induced by immunisation with bovine type II collagen, was studied in Eae39 congenic and sub-interval congenic mice. Antibody titres were investigated with ELISA. Gene-typing was performed by micro-satellite mapping and statistics was calculated by standard methods. Results: Experiments of CIA in Eae39 congenic- and sub-interval congenic mice, carrying RIIIS/J genes on the B10.RIII genetic background, revealed three loci within Eae39 that control disease and anti-collagen antibody titres. Two of the loci promoted disease and the third locus was protected against CIA development. By further breeding of mice with small congenic fragments, we identified a 3.2 mega base pair (Mbp) interval that regulates disease. Conclusions: Disease-promoting and disease-protecting genes within the Eae39 locus on mouse chromosome 5 control susceptibility to CIA. A disease-protecting locus in the telomeric part of Eae39 results in lower anti-collagen antibody responses. The study shows the importance of breeding sub-congenic mouse strains to reveal genetic effects on complex diseases.
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The B10.RIII mouse strain develops collagen-induced arthritis after immunization with bovine collagen type II, whereas the MHC-matched RIIIS/J mouse strain is resistant to arthritis development.
“After immunization with bovine collagen type II (CII), the B10.RIII mouse strain develops CIA, whereas the MHC-matched RIIIS/J mouse strain is resistant to arthritis development.”
From The oncoprotein TBX3 is controlling severity in experimental arthritis (2019) · cites this paper as [8]
The Eae39 locus on mouse chromosome 5 was previously linked to experimental autoimmune encephalomyelitis and also influences collagen-induced arthritis development and severity.
“The genetic locus Eae39, located on mouse chromosome 5, was previously linked to experimental autoimmune encephalomyelitis (EAE), an experimental model for multiple sclerosis. Subsequently, it was also shown to influence CIA development and severity [8, 10].”
From The oncoprotein TBX3 is controlling severity in experimental arthritis (2019) · cites this paper as [8]
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“Subsequently, it was also shown to influence CIA development and severity [8, 10].”
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Self-citation
- Authors
- Lindvall, T., Karlsson, J., Holmdahl, R., & Andersson, Å.
- Affiliations
- Lund University (SE)
- University of California, Los Angeles (US)
- University of Copenhagen (DK)
- Corresponding author
- Lindvall, Therese
- Venue
- Arthritis Research & Therapy
- Published
- 2009-01-20
- Volume
- 11
- Issue
- 1
- Pages
- R10-R10
- ISSN
- 1478-6354 (ISSN-L)
- PMC
- PMC2688241
- OpenAlex
- W2066321776
- Cited by
- 8
- References
- 36
- Citations by year
- 2019: 1 · 2018: 2 · 2014: 1 · 2012: 2
- FWCI
- 0.94
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Arthritis Research & Therapy (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Lund University Publications (Lund University) (submittedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
- Funders
- Crafoordska Stiftelsen
- Novo Nordisk
- Novo Nordisk Fonden
- Topics
- Health Sciences › Medicine › Rheumatology › Rheumatoid Arthritis Research and Therapies
- Health Sciences › Medicine › Rheumatology › Systemic Lupus Erythematosus Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Keywords
- collagen-induced arthritis, mouse chromosome 5, congenic mice, quantitative trait loci, experimental autoimmune encephalomyelitis, H-2 complex, gene mapping
- MeSH terms
- Animals, Antibody Formation, Arthritis, Experimental, Cattle, Chromosomes, Enzyme-Linked Immunosorbent Assay, Mice, Inbred C57BL, Genetic Predisposition to Disease, Collagen Type II, Mice
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