MDR1
This topic is for interested owners and breeders of Shar-Pei. The reason for delving into it is the strong evidence that this genetic disorder has contributed to mutation of the genetic code in Shar-Pei as well.

It is known that this mutation exists in Collies, Border Collies, Shetland Sheepdogs (Shelties), Australian Shepherds, Bobtails, and other breeds. Until recently, I was unaware of this mutation in Shar-Pei dogs. Now I have found reports indicating that even Shar-Pei dogs are among breeds endangered by this genetic disorder. Apparently, some of them have even died from the toxic consequences of this defect.

This genetic disorder results in excessive levels of drugs like Ivermectine, Doramectine, Moxidectine, and Loperamide in the dog’s central nervous system, possibly leading to death.

MDR1 is a member of the ATP binding cassette (ABC) transporter family. The MDR1 protein called p-glycoprotein is membrane-bound and comprises 1,280 amino acids possessing several intracellular and extracellular loops. P-glycoprotein was discovered in the early 70s in cancerous cells resistant to several cytostatic drugs. The term MDR was coined to define this phenomenon of multidrug resistance.  

The MDR1 gene is now known to function as a transporter in the endothelial cells of brain tissue at the blood-brain barrier (BBB). It identifies foreign substances like Ivermectine that enter the endothelial membrane from the blood, and pumps these back into capillaries. This action thus blocks the transfer of foreign substances into surrounding nerve tissue, since the function of a BBB is to protect the brain from being flooded with potentially toxic substances.  

The MDR1 protein is present throughout the body. It is expressed not only at the BBB, but also in the placenta’s syncytio-trophoblast and the endothelial tissue of the blood-testis barrier. In addition, the MDR1 transporter is an effective absorber of drugs and foreign substances in the intestine and plays a vital role in the excretion of drugs via the liver and kidneys. Lack of the complete MDR1 protein allows excessive accumulation of many drugs in the organism.

It is advisable to screen your dog for this problem, since there is strong evidence that this genetic disorder can result in oversensitivity of the animal to other medications too. If you are a breeder, a future puppy owner, and/or current owner of a Shar-Pei, I recommend that you visit the following site: http://www.mdr1-defekt.de/. This site was set up as an initiative to guide concerned breeders, urging them to not only consider typical health issues but also the MDR1 mutation as another criterion when pursuing their dog breeding hobby.

The DNA screening test for an nt230 (del4) MDR1 mutation is conducted by the Institute of Pharmacology and Toxicology, Faculty of Veterinary Medicine, Justus-Liebig University of Gießen.

This is a simple and easy way for vets, breeders, and dog owners to identify Ivermectine oversensitivity. The test is suitable for dogs of all ages and breeds, but not for other small or large animals. Simply go to your vet and have a 1 ml EDTA whole blood sample taken for the check. Send the sample in a padded envelope to:

Institut für Pharmakologie und Toxikologie
MZI 636, MDR1-Defekt beim Collie
Frankfurter Str. 107
35392 Gießen
Germany

http://www.vetmed.uni-giessen.de/pharmtox/mdr1_defekt.html

This Gießen group is a leader in Europe in diagnostics of the genetic mutation in dogs. My recommendation to anyone considering buying a puppy is to demand that the breeder present the results of an nt230 (del4) MDR1 mutation screening test conducted on the puppy and its parents.

Copyright © 2002-2007 Hanspeter Kobold. All rights reserved.