Spontaneous lupus-like syndrome in HLA-DQ2 transgenic mice with a mixed genetic background

S. Rashtak, E. Marietta, S. Cheng, M. Camilleri, M. Pittelkow, C. David, Joseph Peter Grande, Joseph A Murray

Research output: Contribution to journalArticle

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Abstract

To investigate the role of HLA-DQ2 in the pathogenesis of associated immune disorders, we generated transgenic mice that expressed HLA-DQ2 in the absence of endogenous murine class II molecules (AE0DQ2). These AE 0DQ2 mice with a mixed genetic background spontaneously developed skin lesions on their ears, whereas control AE0DQ6 genotype control mice (also with a mixed genetic background) did not. The skin lesions were characterized by deep subepidermal blistering with hydropic degeneration and lymphoid infiltration in the subepidermal area as determined by histopathology. Immunofluorescence analysis revealed thick band-like granular deposition of IgG, IgM, and a thin band of IgA deposition along the basement membrane. AE 0DQ2 mice also developed significant and progressive hematuria and proteinuria as compared with the AE0DQ6 mice (p < 0.05). Histopathology showed immune complex deposits in the glomeruli of AE 0DQ2 mice. Immunofluorescence analysis showed progressive mesangial and capillary wall deposition of IgA, IgM, IgG and C1q in the kidney. With electron microscopy, the deposits showed a 'fingerprint' substructure; and tubuloreticular structures were identified within endothelial cells. Conversely, these changes were not observed in AE0DQ6 mice. Serum anti-double stranded (ds)DNA IgM and IgG levels were also significantly elevated among AE0DQ2 mice compared with AE0DQ6 mice (p < 0.001). In conclusion, AE0DQ2 mice spontaneously develop an autoimmune lupus-like syndrome and are useful model for this disease. It remains to be determined whether genetic admixture played a role in the development of this systemic lupus erythematosus-like syndrome in HLA-DQ2 transgenic mice.

Original languageEnglish (US)
Pages (from-to)815-829
Number of pages15
JournalLupus
Volume19
Issue number7
DOIs
StatePublished - Jun 2010

Fingerprint

Transgenic Mice
Immunoglobulin M
Immunoglobulin G
Immunoglobulin A
Fluorescent Antibody Technique
Genetic Background
Skin
Immune System Diseases
Dermatoglyphics
Hematuria
Antigen-Antibody Complex
Proteinuria
Basement Membrane
Systemic Lupus Erythematosus
Ear
Edema
Electron Microscopy
Endothelial Cells
Genotype
Kidney

Keywords

  • Autoimmune
  • Glomerulonephritis
  • HLA-DQ2
  • Lupus
  • MHC class II
  • Mice
  • Transgenic

ASJC Scopus subject areas

  • Rheumatology

Cite this

Rashtak, S., Marietta, E., Cheng, S., Camilleri, M., Pittelkow, M., David, C., ... Murray, J. A. (2010). Spontaneous lupus-like syndrome in HLA-DQ2 transgenic mice with a mixed genetic background. Lupus, 19(7), 815-829. https://doi.org/10.1177/0961203309360546

Spontaneous lupus-like syndrome in HLA-DQ2 transgenic mice with a mixed genetic background. / Rashtak, S.; Marietta, E.; Cheng, S.; Camilleri, M.; Pittelkow, M.; David, C.; Grande, Joseph Peter; Murray, Joseph A.

In: Lupus, Vol. 19, No. 7, 06.2010, p. 815-829.

Research output: Contribution to journalArticle

Rashtak, S, Marietta, E, Cheng, S, Camilleri, M, Pittelkow, M, David, C, Grande, JP & Murray, JA 2010, 'Spontaneous lupus-like syndrome in HLA-DQ2 transgenic mice with a mixed genetic background', Lupus, vol. 19, no. 7, pp. 815-829. https://doi.org/10.1177/0961203309360546
Rashtak S, Marietta E, Cheng S, Camilleri M, Pittelkow M, David C et al. Spontaneous lupus-like syndrome in HLA-DQ2 transgenic mice with a mixed genetic background. Lupus. 2010 Jun;19(7):815-829. https://doi.org/10.1177/0961203309360546
Rashtak, S. ; Marietta, E. ; Cheng, S. ; Camilleri, M. ; Pittelkow, M. ; David, C. ; Grande, Joseph Peter ; Murray, Joseph A. / Spontaneous lupus-like syndrome in HLA-DQ2 transgenic mice with a mixed genetic background. In: Lupus. 2010 ; Vol. 19, No. 7. pp. 815-829.
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