Update: research on liver shunts, October 2019

A congenital 'extrahepatic portosystemic shunt' is a common problem in many dog ​​breeds. A post-systemic shunt is an additional, inborn blood vessel which connects the portal vein directly to one of the major veins leading to the heart, thereby bypassing the liver and preventing the blood from being cleaned.  

Over the past few years we've made enormous progress in our search for the genetic background of extrahepatic portosystemic shunts. Using Cairn terriers as an example, we found a relation between the disease and two different genes. This same relation was confirmed in Yorkshire terriers, West Highland White terriers, Jack Russell terriers, Miniature Schnauzers en Shih Tzu proving an identical genetic cause. We would now like to extend our research, in order to confirm these initial findings.

Frank van Steenbeek gives the latest update on his research in the video. The second video is subtitled in English, but you can also read up on what Frank says by reading on: 

"Thanks to a great number of contributions from many dog lovers, we have been able to take huge steps forward in our ‘liver shunt' research. We now know that it is a genetic disorder and that it is most likely caused by two genes. We also know which two genes are responsible. However, the complicated part is that the disorder is caused by a combination of these two genes. That makes it harder for us to determine the nature of those genes and the process behind the disorder. But we’ve made great strides forward, which I'd like to explain using an example. Imagine this is the healthy situation. There are ‘on-off switches'. And in those ‘on-off switches', a mutation might occur. But there’s no change. Another mutation might occur. Still no change. But the problem with this disorder is that it’s probably caused by the combination of two mutations. Even though we don't know exactly how they work together, the light comes on, so it's a problem. So that is what we're currently working on. We’re using cells from blood vessels of dogs, in order to see how those genes switch 'on and off’.

 

We’re currently using blood vessel cells situated on the inside of the blood vessel. We also know approximately where those 'on and off buttons' are located. We have now seen a number of mutations within those 'on and off' buttons and are trying to prove that if we stimulate these ‘on-off switches', so effectively turning them 'on', we would see more blood vessels forming from those blood vessel cells. Equally, if we were to turn them ‘off', they wouldn’t be showing the expected function anymore. That's what we're investigating in the lab at the moment.

 

The next step is something that we WANT to do but also something we really NEED to do. We need to understand how these ‘on-off switches' work and find out what happens to the blood vessel development, if we turn those ‘on-off switches’ in the blood vessel ‘on’ or ‘off’. To achieve this, we’re using canine blood vessel cells. That way, we’ll be able to understand how the ‘on-off switches’ of the two genes work together and end up causing the disorder. So that’s what we’re hoping to focus on as a next step.  

 

Thank you so much for your support."