St. Vincent’s Hospital Immunology Centre Mouse Model
From February 2000 to August 2008, The Gutsy Group provided $131,250 to fund the St. Vincent’s Hospital Immunology Centre Mouse Model. This project centered on a mouse model that mimicked human ulcerative colitis.
The research was carried out under the direction of Professor Tony d’Apice, Professor of Immunology at St. Vincent’s Hospital. The Professor’s main research was humanising mice and pigs so animal kidneys may be successfully transplanted into humans in the future. Mice were therefore inserted with the human gene 1-2 fucosyltransferase in the course of different research. Unexpectedly, and through serendipity, these mice developed colitis. As a result, this event enabled extensive research into the mechanism of the colitis to be performed on this animal model over the next nine years.
This research was conducted by four research fellows being Dr. Ashley Miller, Dr. Steven Brown, Dr. Greg Moore and Dr. Mark Lust, all of whom were awarded PhD’s for their research, and three of the researchers received gold medals for this research into gastroenterology. Through this research, it was demonstrated as a world first, that these mice had abnormal thymus glands with consequent major effects on the immune system
Click here for further detail about the research findings from The Mouse Model of Ulcerative Colitis.
The Mouse Model of Ulcerative Colitis
In the transgenic Mouse Model of Ulcerative Colitis (hFUT1), the human gene for Alpha 1 -2 fucosyltransferase, inserted into the normal DNA of the mouse, produced spontaneous colitis that was similar to the human disease, ulcerative colitis. The mice developed severe diarrhoea, wasting and early death.
As a result of extensive research with the model, it was found that this genetic manipulation changed the type and shape of the sugar molecules that protruded from the surface of many cells, including lymphocytes, which are the major cells that control immunity. It was found that this abnormality caused:
- Chronic inflammation of the colon;
- Defect in the mucus produced by the colon (mucus is thought to be a factor in preventing bacteria from invading the wall of the colonoscopy);
- Aberrant development of lymphocytes. Immature lymphocytes are processed by the thymus gland, which lies in front of the heart. Normal lymphocytes pass through the thymus, and have a number of sugar molecules attached to their surface, and then circulate back into the tissues of the body so they can carry out their normal immune function. In this mouse model the thymus gland was small and under-developed, (atrophic), and consequently the lymphocytes had abnormal surface markers, and therefore loss of their normal immune function.
This is the first time that an animal model of colitis had been developed due to a thymic abnormality.
It was found that the colitis in this model could be reversed by irradiating the mice, and transplanting normal immune system using bone marrow from a normal mouse. Furthermore, if the abnormal mice were bred in a germ-free environment, (have no bacteria in the gut), they did not develop colitis.
Finally, many experiments were performed to detect coagulation abnormalities, but no significant defects were identified.
Further information can be found in the articles published in the Inflammatory Disease Journal
Brown, S.J., Miller A.M., Cowan P.J., Slavin J, Connell W.R.,. Moore G.T., Bell S., Elliott P.R., Desmond P.V., d’Apice A.J., “Altered Immune System Glycosylation Causes Colitis in Alpha1,2-fucosyltransferase Transgenic Mice”, Inflammatory Bowel Disease 2004 Sep; 10(5):546-56.
Moore, G.T., Brown, S.J., Winterhalter A.C., Lust M., Salvaris E.J., Selan C., Nandurkar H.H, Desmond P.V., Cowan P.J., d’Apice A.J., “Glycosylation Changes in hFUT1 Transgenic Mice Increase TCR Signaling and Apoptosis Resulting in Thymocyte Maturation Arrest”, Mol. Immunology 2008 Apr; 45(8):52401-2410.
Health Economics Group – Cost of Inflammatory Bowel Disease in Australia
In 2005 and 2006 The Gutsy Group provided funding of $20,000 to the Health Economics Group at The University of Melbourne. The analysis was carried out by Stephen Colgan, the research fellow with the Health Economics Group Programme Evaluation Unit, under the tutelage of Associate Professor Rob Carter. This research was undertaken to assess the financial burden of inflammatory bowel disease in Australia, to highlight the future impact of IBD, and to assist in the raising of funds.
The final report on the cost of inflammatory bowel disease was tabled in March, 2006. The report was the first comprehensive assessment of the costs of IBD in Australia and the most complete economic assessment. of the burden of the disease. Some of the key findings were:
- The prevalence of IBD in Australia was 360 per 100,000, which second highest only to Canada.
- The total cost of IBD in Australia in 2005 was approximately, $267 million, $220 million related to medical costs, and $40 million to lost wages.
Please contact us if you would like to obtain a copy of the report.
Geelong Incidence Study
In 2007 and 2008, in conjunction with the Bennelong Foundation, The Gutsy Group contributed $70,000 to a study undertaken by research fellow, Dr. Jarrad Wilson from the Department of Gastroenterology at St. Vincent’s Hospital, Melbourne to produce the first prospective population-based Australian incidence and study of inflammatory bowel disease.
As a result of this research, Dr. Jarrad Wilson was awarded the gold medal in 2008 by the Gastroenterological Society of Australia for the best clinical research for a junior investigator.
The report is titled “High Incidence of Inflammatory Bowel Disease in Australia: A Propsective Population Based Australian Incidence Study” and will shortly be published in 2010
The research was carried out in Greater Geelong, Victoria. The risk population was 259,000, and all 274 general practitioners and specialists working in this area were contacted every 2 months to identify all new cases occurring on one year. The results were:
- 75 new cases of inflammatory bowel disease – 46 Crohn’s disease and 29 ulcerative colitis. The peak incidence occurred between the ages of 20 and 24 years, with 42 females and 33 males.
- The inflammatory bowel disease incidence rate of 29.3 per 100,000 is the second highest ever reported in the literature, and the Crohn’s disease incidence rate of 17.8 per 100,000 is the highest ever reported.
