Mice lacking endogenous major histocompatibility complex class II develop arthritis resembling psoriatic arthritis at an advanced age

Tamas BARDOS; Jian Zhang; Katalin MIKECZ; Chella S DAVID; Tibor T GLANT

doi:10.1002/art.10637

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Mice lacking endogenous major histocompatibility complex class II develop arthritis resembling psoriatic arthritis at an advanced age

Journal article

Peer reviewed

Mice lacking endogenous major histocompatibility complex class II develop arthritis resembling psoriatic arthritis at an advanced age

Tamas BARDOS, Jian Zhang, Katalin MIKECZ, Chella S DAVID and Tibor T GLANT

Arthritis and rheumatism, Vol.46(9), pp.2465-2475

2002

DOI: 10.1002/art.10637

PMID: 12355495

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Abstract

Objective: To describe and characterize a novel inflammatory toe disease with severe bone destruction that developed spontaneously in "humanized" (HLA transgenic) mice lacking their own major histocompatibility complex (MHC). Methods: We studied 5 different HLA transgenic mouse lines (HLA-DR2.Ab(0), DR3.Ab(0), DR4.Ab(0), DQ6.Ab(0), and DQ8.Ab(0)) in similar genetic background for an extended period of time (>14 months). Clinical, radiologic, and histologic abnormalities were monitored, and the MHC-related major immunologic parameters in affected and resistant mice were compared. Results: Animals of 4 transgenic lines (HLA-DR2.Ab(0), DR4.Ab(0), DQ6.Ab(0), and DQ8.Ab(0)) developed severe toe inflammation accompanied by progressive bone resorption, hyperkeratosis, alopecia, loss of nails, and shortening and thickening of the distal phalanges. HLA-DR3.Ab(0) transgenic mice were resistant to inflammation. The disease manifested only at advanced ages (6 months or older) and affected 70-100% of the mice, with a female preponderance. The clinical signs and the radiographic and histopathologic features of the affected toes were not similar to those of any disease previously described in mice but did resemble those described for human psoriatic arthritis (PsA). Mice from the 4 susceptible lines expressed lower levels of the HLA transgene and exhibited significantly fewer CD4+ cells in the peripheral blood and reduced natural killer cell activity compared with mice from the resistant HLA-DR3.Ab(0) line. Conclusion: This novel, spontaneously developing PsA-like toe disease in MHC-manipulated mice seems to be related to the absence of endogenous MHC class II. Replacement with HLA transgene expression that is insufficient (or no replacement at all) may result in imbalanced MHC class I and class II functions and lead to development of the disease.

Inflammatory joint diseases

Biological and medical sciences

Medical sciences

Diseases of the osteoarticular system

Details

Title: Subtitle: Mice lacking endogenous major histocompatibility complex class II develop arthritis resembling psoriatic arthritis at an advanced age
Creators: Tamas BARDOS - University of Pécs, Pécs, Hungary
Jian Zhang - Rush University at Rush-Presbyterian-St. Luke's Medical Center, Chicago, Illinois, United States
Katalin MIKECZ - Rush University at Rush-Presbyterian-St. Luke's Medical Center, Chicago, Illinois, United States
Chella S DAVID - Mayo Clinic Foundation, Rochester, Minnesota, United States
Tibor T GLANT - Rush University at Rush-Presbyterian-St. Luke's Medical Center, Chicago, Illinois, United States
Resource Type: Journal article
Publication Details: Arthritis and rheumatism, Vol.46(9), pp.2465-2475
DOI: 10.1002/art.10637
PMID: 12355495
NLM abbreviation: Arthritis Rheum
ISSN: 0004-3591
eISSN: 1529-0131
Publisher: Wiley; Hoboken , NJ
Grant note: name: NIH, award: AR-40310, AR-45652, AI-14764
Language: English
Date published: 2002
Academic Unit: Pathology
Record Identifier: 9984047678102771

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