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Obesity is a growing health problem in the industrialised countries. Especially cardiovascular diseases and type II diabetes are closely linked to a high body mass index (BMI). Humans with a BMI above 40 are considered morbidly obese. Apart from diet and lack of exercise also genetic predisposition is a major factor in obesity. Various genes have been studied to elucidate the role in increased body weight. The fat mass and obesity associated gene (FTO) is located on human chromosome 16. While the phenotypic association is clear, the physiological basis is poorly understood. FTO contains a nuclear localisation signal and shows a ubiquitous expression pattern including metabolically relevant tissues such as pancreas, liver and the hypothalamus. The present invention provides non-human mammals with partial or total disruption of the FTO gene or protein function. The invention provides model animals for studying the functional role of FTO. It further provides mammalian cells for high throughput screening of agents modifying the function of FTO.
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