Prion Protein – TSEs

00:01 So let’s talk a little bit about the gene itself encoding this PrPc protein.

00:05 Remember I said it is a normal cell protein in you, it is encoded by a gene, like all proteins are.

00:12 The gene is called prnp, so PrPc is encoded by the prnp gene, it has a normal cellular function. In animals we can give animals, experimentally in the laboratory, these TSEs, by inoculating them with homogenates of brains from people who have died of the disease.

00:35 We don’t usually do this with people, we will take a sheep with scrapie, or a cow with BSE. We will grind up their brains, we inoculate it into an animal like a mouse or hamster, sometimes we can transmit the disease to another species. So this is the basis for what I’m going to tell you for the next few slides.

00:53 If you take a mouse, and let’s say you have a mouse that developed the TSE for whatever reason. You grind up its brain, you inject it into another mouse, that mouse will develop a TSE. However, if you delete the prnp gene from that recipient mouse, and we can do this genetically relatively easily, you can make a knockout mouse recall for both copies of the gene, remember we have two copies of most of our genes, that mouse now will not develop a TSE when you inject PrPsc right into its brain. So the prnp gene is essential to develop a TSE. Think about it, it makes sense, if you don't have any PrPc protein in you, there's no way that a little bit of PrPsc that you acquire can cause disease, because it doesn’t have any PrPc to convert to the pathogenic protein. Now we can’t delete genes in people, otherwise that would be one way of preventing TSEs. But it could be that in us, we need this prnp genes. So it is probably not a good strategy. Alright, so now you need to remember prnp is essential for a TSE.