Genetics of monogenic obesity 2

Published on December 31, 2015   28 min

Other Talks in the Series: Obesity: Science, Medicine and Society

Other Talks in the Series: Molecular Genetics of Human Disease

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My name is Anke Hinr. I'm going to present you some additional data pertaining to monogenic forms of obesity. In the first part, you already heard a lot of data pertaining to the major gene for obesity, the leptin gene, with mutations usually leading to severe forms of extreme obesity. And now we've switched to a gene, which is working in the same cascade of the weight regulation. It's called the melanocortin-4 receptor gene.
The leptin signal is received in the central regions of the brain. And the melanocortin-4 receptor is one of the effectors of this leptin signal. In 1997, the first knockout mouse model was published, showing the relevance of this gene for body weight regulation.
Mice not expressing this receptor or only heterozygously expressing the receptor, and you can see the weight charts of these mice, on the upper part of this slide, you can see the females with the lack of this receptor. And in the lower part of this slide, you can see the male mice not harboring or only harboring one copy of this melanocortin-4 receptor. So if you look at the upper part, then you see the weight development of the wild type mice, indicated by the +/+ sign. And on the other hand, the -/- or +/- mice display much higher weight than the wild typic mice. And you can also see that the heterozygous mice, the weight of these mice are sort of in between, at least in the female sex, in between the knockout, in the wild type mice, and for the males there is an overlap between the wild type and the heterozygous. This also already indicated that mutations in this gene leads to a dominant form of obesity. So lack of one copy of this gene is already sufficient to lead to an increased body weight. And in the meantime, a lot of mutation screens had been performed for this gene. And a lot of obese and normal weight individuals had been screened for mutation.