Pathophysiology and Etiology of a Novel Mouse Model for Vasculitis

Kendrick Key

Document Type

Article

Publication Date

8-9-2024

Keywords

JMG

JAX Location

In: Student Reports, Summer 2024, The Jackson Laboratory

Abstract

Vasculitis is a heterogeneous group of disorders defined by blood vessel inflammation and tissue damage (1). Preliminary data suggest that Collaborative Cross Recombinant Inbred Cross (CCRIX) mice developed a rare form of small-vessel vasculitis known as Granulomatosis with Polyangiitis (GPA). The mice presented with kidney failure leading to early death. This prognosis mirrors clinical observations, where up to 90% of patients with untreated GPA patients die of respiratory or kidney failure within 2 years. GPA patients initially show a range of respiratory symptoms, fever, and malaise followed shortly by severe damage to the ears, eyes, throat, lungs, or kidney. This diverse range of symptoms necessitates extensive characterization of clinical and subclinical features for an accurate differential diagnosis (2). The lack of models for GPA slows the discovery of biomarkers and targeted therapeutics that would improve diagnosis and treatment. CCRIX-GPA mice provide an important opportunity to do this through a better understanding of GPA genetics and disease mechanisms. Here we used a range of clinical and genomic assays to define the disorder. GPA Pathophysiology was characterized via glomerular filtration rate analysis, urinalysis, gross necropsy, and histopathological analysis of collected tissue samples. GPA etiology was investigated via RNA-sequencing analysis. This process will lead to a complete and accurate diagnosis of the vasculitis and allow us to detect the early stages of disease in live mice. These data will be critical for follow up studies that test disease mechanisms or treatments for GPA.

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