A unique model of inflammatory bowel disease.

炎症性肠病(IBD)有两种临床形式，即溃疡性结肠炎(UC)和克罗恩病(CD)。这些都是主要影响年轻人的严重疾病。它们有时是致命的，往往会严重削弱身体。UC的治疗通常需要切除大肠并终生佩戴回肠造口袋。虽然这是治愈的，但其心理和生活方式的影响非常令人不安，特别是在年轻人。IBD的原因尚不清楚，尽管很明显，遗传和环境因素都有。我们已经在小鼠身上开发了一种IBD模型，看起来非常像人类UC。我们已经培育出转基因小鼠，它们的肠壁分泌的粘液似乎与正常小鼠不同。我们建议调查这种变化是如何导致UC的。很可能是粘液有缺陷，无法阻止粪便中的一些正常细菌或其他物质进入肠壁，导致慢性炎症。如果我们能证明情况是这样的，它就有力地支持了这样的观点，即一些人可能会出现类似的遗传特征，这可能是使他们容易患IBD的遗传成分之一。换句话说，这将是一种可能导致人类易感性的基因缺陷类型的指示器，因此有助于集中寻找基因成分。了解疾病易感性背后的遗传因素对于遗传咨询至关重要。此外，了解导致IBD的各种因素对于开发针对病因而不是针对疾病症状的合理治疗至关重要。

Inflammatory Bowel Disease (IBD) has two clinical forms known as Ulcerative Colitis (UC) and Crohn's Disease (CD). These are severe diseases which predominantly affect young people. They are occasionally fatal and often severely debilitating. Treatment of UC frequently requires removal of the large bowel and life long wearing of an ileostomy bag. While this is curative, its psychological and life style effects are very disturbing particularly in the young. The cause of IBD is unknown, although it is clear that there are both genetic and environmental factors. We have developed a model of IBD in mice which appears to be very like human UC. We have generated genetically modified mice in which it appears that the mucous secreted by their bowel wall is different from normal. We propose to investigate how this change leads to UC. It appears likely that the mucous is defective and can not prevent some of the normal bacteria or other material present in the stools from entering the bowel wall and causing chronic inflammation. If we can show that this is the case, it adds strong support to the the idea that a similar genetic trait may occur in some humans and that this may be one of the genetic components which renders them susceptible to IBD. Put another way, it would be a pointer to the type of genetic defect which may underlie susceptibility in humans and so help to focus the search for the genetic component. Understanding genetic factors underlying disease susceptibility is vitally important to inform genetic counselling. In addition, understanding the various factors which lead to IBD is critical to developing rational treatments which target cause rather than the symptoms of the disease.