Spontaneous Models of Human Disease
EuroSciCon - London, February 2nd 2007
The aim of this meeting, held by Euroscicon, was to check the state-of-the-art about the novel findings on the pathogenic mechanisms of human diseases and immunotherapy.
The excellent speakers provided very interesting updated information on the use of animal models developing spontaneous diseases. Using experimental and transgenic models is necessary to unravel human pathological processes. Valid animal models of diseases are of greater importance to better clarify human disease molecular pathways and to provide newer target for potential pharmacological treatment. Nowadays, we have lots of “artificial” models (i.e. genetic mice, chimeras) providing information about “natural” regulatory mechanisms that could indicate novel potential therapeutic targets.
The non-obese diabetic (NOD) mouse model is an excellent animal model of human autoimmune diseases, providing information on the effects of infection on the regulation of Type 1 diabetes. Regulatory T cell therapy could offer many potential advantages for the diabetic care.
Another excellent animal model is the humanized animal model of autoimmune thyroiditis TAZ10. TAZ10 mice spontaneously develop autoimmune hypothyroidism with histological, hormonal and clinical signs similar to the human pathology. This new 'humanized' model will provide a unique tool to investigate how human pathogenic self-reactive T cells initiate autoimmune diseases and to determine how autoimmunity can be modulated in vivo.
Other very important experimental models to unravel human diseases are the autoimmune encephalomyelitis model to study multiple sclerosis, the induced models of rheumatoid arthritis, the DQ8 transgenic mice with intestinal gliadin hypersensitivity to study the celiac disease, the spontaneous mouse myodystrophy mutant is a valid model for human dystroglycanopathies. Studies of experimental autoimmune encephalomyelitis in conventional and transgenic mouse models have clarified mechanisms of central and peripheral tolerance to myelin antigens. Collagen-induced arthritis is the most widely used animal model for the evaluation of novel therapeutic strategies for rheumatoid arthritis.
In the spontaneous model of Duchenne muscular dystrophy, novel therapies are promising: delivery of recombinant versions of the DMD gene using viral or non-viral vectors is showing good results in pre-clinical experiments.
The autoimmune lymphoproliferative syndrome is a genetic disease of immune homeostasis. An important result is that the cellular homeostasis and tolerance in human is under the control of apoptosis. Modulation of apoptotic pathways by animal models may provide new insights in this field.
Mouse models with well defined mutations are essential to unravel complex molecular mechanisms.
The mouse models of immunodeficiency and immunophathogenesis by conditional mutagenesis in myeloid and lymphoid lineages, and mouse models for arteriosclerosis have provided genetic basis for these diseases, opening future ways for better therapies.
author: Dr. Dario Siniscalco, Department of Experimental Medicine, Second University of Naples, Naples, Italy. dariosin@uab.edu
posted by: Dr. Claire Morgan, claire.morgan@euroscicon.com
