Spontaneous IgM glomerulopathy in female athymic nude sentinel mice

Abstract

Female Hsd:Athymic nude-Foxn1 ^nu sentinel mice spontaneously develop a life-limiting protein-losing nephropathy. We aimed to characterize this disease and identify risk factors. Affected mice presented with anasarca and pale tan, irregularly pitted kidneys. Histologically, glomeruli were distorted by eosinophilic, hyaline, mesangial deposits. Additional non-specific glomerular changes included synechiae, periglomerular fibrosis, and capillary thrombosis. Ectatic tubules with attenuated epithelium and tubular casts and interstitial inflammation were also present. Mesangial deposits were Congo red (CR)-negative, periodic acid-Schiff-positive, and pale blue to pink using Masson’s trichrome stain. The glomerular basement membrane was mildly irregular using Jones’ methenamine silver stain. The mesangial deposits were immunoglobulin G (IgG)- and immunoglobulin A (IgA)-immunonegative and immunoglobulin m (IgM)-immunopositive. Ultrastructurally, subendothelial electron-dense deposits were composed of straight and curved linear, 30 to 170 nm diameter tubular, and 9 to 16 nm diameter fibrillary profiles. Together, these findings were consistent with hyaline glomerulopathy due to IgM deposition. Prevalence of the disease over 6 years was 0.6% (75/13 042 homozygous sentinel mice). Vivarium biosecurity level, infectious disease screening results, and comorbidities were evaluated in 75 female, 6-month-old, homozygous nude sentinel mice with hyaline glomerulopathy and 75 without. Neither biosecurity level nor pathogen diversity was risk factors. However, sentinel mice with auto-inflammatory conditions, such as proliferative typhlocolitis (P = .005) and dermatitis (P = .03), and with lymphoid neoplasia (lymphoma; P = .0007) had a lower risk of developing hyaline glomerulopathy. Our results support the diagnosis of hyaline glomerulopathy in young adult, female, nude sentinel mice and help recognize this spontaneous condition in a canonical immunodeficient research model.