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The RHJ/Le rhino mutant: description of a unique murine model of autoimmunity
R D Roberts1, A B Kier, S E Walker
1University of Missouri-Columbia, MO.
Abstract:
The BALB/c HuDI-hrrh rhino mutant, which is no longer available, was an unusual murine model with prominent hepatic inflammation and fibrosis. The current report describes the early appearance of hepatic portal tract inflammation and antinuclear antibodies in the RHJ/Le mouse, a related rhino mutant which is distributed from a commercial source. All homozygous RHJ/Le rhino (hrrh hrrh) mice examined serially from 2 to 18 months of age developed inflammation of hepatic portal tracts. In 81 per cent of mice, portal and central veins were infiltrated with mononuclear cells. Focal infiltrates were found in salivary, Harderian and lacrimal glands and in the pancreas. Isolated animals had myositis involving skeletal muscle and myocardium. Heterogeneous antinuclear antibodies were detected in sera from 100 per cent of rhino mice and antibodies to DNA were present in 28 per cent of mice aged 6 months. Homozygous HRS/J hairless (hr/hr) and BALB/c controls failed to show consistent abnormalities in exocrine glands or liver. We conclude that the RHJ/Le rhino mutant spontaneously develops antinuclear antibodies and mononuclear cell infiltration in liver and exocrine glands. These animals provide unique opportunities to examine inflammatory lesions localized to specific target organs in an animal model of autoimmunity.
Insights
The RHJ/Le rhino mutant mouse spontaneously develops liver inflammation and antinuclear antibodies. This autoimmune model shows mononuclear cell infiltration in multiple organs, offering insights into autoimmune diseases.
Area of Science:
- Immunology
- Pathology
- Genetics
Background:
- The BALB/c HuDI-hrrh rhino mutant, a previously available murine model, exhibited significant hepatic inflammation and fibrosis.
- A related, commercially available rhino mutant, RHJ/Le, is investigated as a potential model for studying autoimmune conditions.
Purpose of the Study:
- To characterize the early onset of hepatic portal tract inflammation and antinuclear antibody production in the RHJ/Le rhino mutant.
- To investigate the distribution of mononuclear cell infiltration in various organs of the RHJ/Le rhino mutant.
- To establish the RHJ/Le rhino mutant as a viable animal model for studying organ-specific autoimmune inflammatory lesions.
Main Methods:
- Serial examination of homozygous RHJ/Le rhino (hrrh hrrh) mice from 2 to 18 months of age.
- Histopathological analysis of liver and exocrine glands to identify mononuclear cell infiltration.
- Serological testing for antinuclear antibodies (ANA) and antibodies to DNA.
Main Results:
- All examined RHJ/Le rhino mice developed hepatic portal tract inflammation.
- Mononuclear cell infiltration was observed in portal and central veins (81% of mice), salivary, Harderian, lacrimal glands, and pancreas.
- 100% of rhino mice had heterogeneous antinuclear antibodies, with 28% positive for anti-DNA antibodies by 6 months.
- No consistent abnormalities were found in control HRS/J hairless (hr/hr) and BALB/c mice.
Conclusions:
- The RHJ/Le rhino mutant spontaneously develops antinuclear antibodies and mononuclear cell infiltration in the liver and exocrine glands.
- This mutant mouse serves as a valuable model for investigating spontaneous autoimmunity and organ-specific inflammatory lesions.