New Mouse Model of AAV May Reveal Role of Specific DNA Regions

New Mouse Model of AAV May Reveal Role of Specific DNA Regions

A new mouse model of ANCA-associated vasculitis (AAV) shows glomerulonephritis, lung vasculitis, and MPO-ANCA autoantibodies, among other alterations seen in patients with the disease. These mice may help determine genetic factors in AAV, the researchers said.

The study, “Vasculitis and Glomerulonephritis in a Newly Established Congenic Mice Strain from ANCA-Associated Vasculitis-prone SCG/KJ Mice,” was presented at the British Society for Rheumatology Annual Conference 2019 in Birmingham, England.

Use of the mouse model of AAV, known as SCG/Kj, has enabled a team from Japan to identify seven quantitative trait loci (QTLs), which refer to DNA regions associated with disease susceptibility.

Aiming to determine the function of each of these DNA spots and discover genes linked to AAV susceptibility, the scientists introduced these QTLs into mice with a different genetic background.

Two of the loci — Scg-1 and Scg-2/Man-1 — were introduced on chromosome 1. Both are expected to lead to glomerulonephritis — inflammation of the glomeruli, the kidney’s filtering units — autoantibody production, and blood vessel inflammation, or vasculitis, while Scg-2/Man-1 is also anticipated to lead to the production of MPO-ANCA antibodies.

The investigators analyzed proteinuria (abnormal amounts of protein in urine), hematuria (blood in urine), and crescentic glomerulonephritis, which refers to extensive glomerular crescents, defined by two or more layers of proliferating cells in the kidney’s Bowman’s capsule. They also analyzed lung vasculitis and levels of serum autoantibodies, among other assessments.

As the researchers expected, the transgenic mice showed MPO-ANCA production and crescentic glomerulonephritis. As in AAV patients, these mice also revealed vasculitis in multiple organs, especially the lungs and the kidneys.

Specifically, vasculitis was characterized by infiltration of immune cells into the blood vessel walls, followed by infiltration of granulocytes, a type of white blood cells.

The blood levels of MPO-ANCA autoantibodies were significantly associated with the severity of glomerulonephritis, crescent formation, and lung vasculitis. The analyses further showed accumulation of MPO in glomeruli, supporting the role of both MPO and MPO-ANCA in disease development in this model. 

“This strain will be useful for elucidating the mechanism of ANCA generation and the pathogenesis of [crescentic glomerulonephritis] and vasculitis, and searching related genetic factors in AAV,” the scientists stated.

José is a science news writer with a PhD in Neuroscience from Universidade of Porto, in Portugal. He has also studied Biochemistry at Universidade do Porto and was a postdoctoral associate at Weill Cornell Medicine, in New York, and at The University of Western Ontario in London, Ontario, Canada. His work has ranged from the association of central cardiovascular and pain control to the neurobiological basis of hypertension, and the molecular pathways driving Alzheimer’s disease.
Total Posts: 11
Inês Martins holds a BSc in Cell and Molecular Biology from Universidade Nova de Lisboa and is currently finishing her PhD in Biomedical Sciences at Universidade de Lisboa. Her work has been focused on blood vessels and their role in both hematopoiesis and cancer development.
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José is a science news writer with a PhD in Neuroscience from Universidade of Porto, in Portugal. He has also studied Biochemistry at Universidade do Porto and was a postdoctoral associate at Weill Cornell Medicine, in New York, and at The University of Western Ontario in London, Ontario, Canada. His work has ranged from the association of central cardiovascular and pain control to the neurobiological basis of hypertension, and the molecular pathways driving Alzheimer’s disease.
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