For years, mouse models have been used to study the course of MS, in the hope of gaining insights regarding this elusive disease. Certain strains of mice have been favoured in studies over others, due to hallmarks expressed during the course of the disease which mimic the human counterpart.
Under the guidance of Dr Jacqueline Orian, Leana Downs, a budding researcher, will investigate a variant of the model which may have potential to mirror the human disease by demonstrating the presence of lesions in the brain before they appear in the spinal cord.
The BALB/C mouse is a well-established variant of Experimental Autoimmune Encephalomyelitis (EAE), a MS-like disease in animals. The literature reports that approximately 60-70% of injected mice develop the clinical disease. Preliminary studies by Leana Downs, from pre-clinical stage, demonstrate that 100% of the mice exhibit inflammation and lesions in the forebrain and cerebellum earlier than in the spinal cord. This project will further characterize the progression of the disease to evaluate the potential of this model for MRI studies of disease progression.
Leana has looked at the brains and spinal cords of BALB/C mice and identified ongoing progressive lesions over the course of the disease. Leanna also characterised inflammation in the spinal cord of these animals and found that the disease peaked at a similar time to other animal models of MS. Interestingly, the clinical score (a measure of the outward symptoms) did not correlate with the disease seen in the brain and is therefore not an accurate marker of disease in this model. The lesions were found in the same regions of the central nervous system across all the animals in the group, making this model consistent – an important feature for its usefulness in scientific work.
Leana also looked at the inflammatory cells present within the lesions. She found two types of lesions were present in the brains. The first type were characterised by inflammatory cells, T cells and B cells, which are immune cells from the bloodstream which have entered the brain tissue. The second type of lesion did not contain inflammatory cells, but showed signs of cellular stress within the nerve cells of the brain. Often, the two types of lesion were located alongside each other, but did not overlap.
Leana has continued to work in Dr Orian’s laboratory after the completion of her project and further investigated this model of MS. She has investigated the effect of pertussis toxin on the animals (the chemical used to induce disease) and found that increasing the dose increases the severity of disease. She also looked at a version of the mouse where the interleukin receptor 4a gene had been deleted. This gene plays a role in inflammation and Leanna found that mice without the gene showed less inflammation than the normal mice. Both of these more recent findings supports the use of this model for studies examining lesion load in MS.
Updated: 25 February 2015
Updated: 02 January, 2011