Spontaneous NOD Mouse for Sjögren’s Syndrome Research

Sjögren’s syndrome is a chronic autoimmune condition in which the moisture-producing glands of the body are attacked and destroyed by the body’s immune system. The disease arises spontaneously in the non-obese diabetic (NOD) mouse model. Unlike type I diabetes, which spontaneously arises in NOD mice with a strong female preponderance, Sjögren’s syndrome spontaneously arises in NOD mice with a male preponderance. From sixteen weeks of age, lymphocytic cell infiltration into the lacrimal glands leads to a progressive loss of secretory function resulting in a decreased production of tears and subsequent dry eye. Lymphocytic cell infiltration also affects the salivary glands, leading to a loss of secretory function and decreased production of saliva.

Study Endpoints

  • Lacrimal gland function assessment (tear production)
  • Salivary gland function assessment (saliva production)
  • Flow cytometry of spleen or lacrimal glands
  • Histopathology

The primary readouts when testing lead compounds with a potential efficacy in Sjögren’s syndrome are the reduced tear production and the reduced salivary flow production measured in vivo. Typically, a 40% reduction in tear production is observed at 22 weeks of age. Additional readouts are measured in vitro. The cellular infiltrate in the lacrimal glands can be characterised and quantified by histopathology and/or flow cytometry.
 

Validation Data

Figure 1: lacrimal gland function assessed by the cotton thread length test

Graph showing lacrimal gland function assessed by the cotton thread length test in dexamethasone and untreated groups

Dexamethasone administered daily at 100 mg/kg shows efficacy on lacrimal gland function, as assessed by cotton thread length test.
 

Figure 2: Histopathology of salivary and lacrimal glands

Figure 3: Flow cytometry of spleen and lacrimal gland immune cells

Flow cytometry of spleen and lacrimal gland immune cells

In the spleen, dexamethasone shows efficacy via a reduction in the level of splenic B cells and plasmablasts. In lacrimal glands, dexamethasone reduces the overall level of CD45+ leukocyte infiltrate and the level of B cells.