LABOKLIN (UK)|Genetic Diseases | Dogs| MDR1 Gene Defect / Ivermectin Sensitivity *

MDR1 Gene Defect / Ivermectin Sensitivity *

Test number: 8032

MDR1

Breeds

Australian Shepherd , Border collie , Collie , English shepherd , German Shepherd , Longhaired Whippet , McNab Shepherd (McNab Border Collie) , Old English Sheepdog (Bobtail) , Shetland Sheepdog (Sheltie) , Silken Windhound , Rough Collie , Smooth Collie , Bobtail , American White Shepherd , Waeller (Wäller) , Elo .

Kennel Club

This test is part of the Official UK Kennel Club DNA Testing Scheme in Australian Shepherd , Border collie , Shetland Sheepdog (Sheltie) , Rough Collie , and Smooth Collie.

The Disease

MDR1 is a genetic disorder found in many dog breeds. Affected dogs, when treated with certain common drugs such as Ivermectin and loperamide (Imodium), are unable to pump out these drugs from the brain resulting in poisoning and neurologic symptoms ranging from tremors, anorexia and excess salivation to blindness, coma and even death. Some of these drugs such as Ivermectins, which vets prescribe extensively for the treatment of parasite infections, are able to cause toxicity at 1/200th of the dose required to cause toxicity in healthy dogs.

Scientists discovered that these dogs lack a protein (P-Glycoprotein), which is responsible for pumping out many drugs and toxins from the brain, and that affected dogs show signs of toxicity because they are unable to stop drugs from permeating their brains. Researchers have identified that this condition is due to a mutation in the multi-drug resistance gene [MDR1].

LIST OF DRUGS THAT CAUSE SENSITIVITY TO DOGS WITH MDR1 MUTATION

Class A

Do not use these drugs in dogs with MDR1 Gene Defect

Ivermectine substances "Anti parasites": (Diapec®, Ecomectin®, Equimax®, Eqvalan®, Ivomec®, Noromectin®, Paramectin®, Qualimec®, Sumex®, Virbamec®)

Doramectine substances "Anti parasites": (Dectomax® )

Loperamide substances "ant diarrheal ": (Imodium®)

Moxidectine substances "Anti Parasites" (Cydectin®, Equest®)

Class B

Use only under close control of veterinarian

Cytostatics "Chemotherapy": (Vinblastine, Vincristine, Doxorubicine, Paclitaxel, Docetaxel, Methotrexat, Vincristine)

Immunosuppressive: (Cyclosporine A)

Heart glycosides: (Digoxine, Methyldigoxine)

Opioids: (Morphium)

Antiarrhythmics: (Verapamil, Diltiazem, Chinidine)

Antiemetics (Ondansetron, Domperidon, Metoclopramide )

Antibiotics (Sparfloxacin, Grepafloxacin, Erythromycin)

Antihistamin (Ebastin)

Glucocorticoid (Dexamethason)

Acepromazine (tranquilizer and pre-anesthetic agent) *

Butorphanol "analgesic and pre-anesthetic agent" *

Other drugs: Etoposide, Mitoxantrone, Ondansetron, Paclitaxel, Rifampicin

Class C

Can be used only in the permitted application form and dose!

Selamectin (Stronghold®), Milbemax® and Advocate® .

* In dogs with the MDR1 mutation, acepromazine and butorphanol tend to cause more profound and prolonged sedation in dogs . It is recommended to reduce the dose by 25% in dogs heterozygous for the MDR1 mutation (MDR1 / N) and by 30-50% in dogs homozygous for the MDR1 mutation (MDR1 / MDR1).

Trait of Inheritance

Dogs that are homozygous for the mutation display, due to a non-functional transporter the ivermectin sensitive phenotype. They can show increased absorption of ivermectin and other substrates e.g. Digoxin, Vincristine, Doxorubicin, Cyclosporin A, Grepafloxacin, Dexamethasone and Loperamide (See list of drugs). Heterozygous animals (carriers) may show sensitivity to avermectins and other drugs. They are able to propagate the responsible mutation throughout the population and it is therefore important that carrier animals are detected prior to breeding.

Inheritance : AUTOSOMAL RECESSIVE trait

Sire

Dam

Offspring

clear
clear

100% clear

clear

carrier

50% clear + 50% carriers

clear

affected

100% carriers

carrier

clear

50% clear + 50% carriers

carrier

carrier

25% clear + 25% affected + 50% carriers

carrier

affected

50% carriers + 50% affected

affected

clear

100% carriers

affected

carrier

50% carriers + 50% affected

affected

affected

100% affected

Clear

Genotype: N / N [ Homozygous normal ]

The dog is noncarrier of the mutant gene.
The dog will never develop MDR1 Gene Defect / Ivermectin Sensitivity * and therefore it can be bred to any other dog.

Carrier

Genotype: N / MDR1 [ Heterozygous ]

The dog carries one copy of the mutant gene and one copy of the normal gene.
The dog may develop MDR1 Gene Defect / Ivermectin Sensitivity.
Since it carries the mutant gene, it can pass it on to its offspring with the probability of 50%.

Affected

Genotype: MDR1 / MDR1 [ Homozygous mutant ]

The dog carries two copies of the mutant gene and therefore it will pass the mutant gene to its entire offspring.
The dog will develop MDR1 Gene Defect / Ivermectin Sensitivity * and will pass the mutant gene to its entire offspring

Description

This is a mutation-based gene test, which offers many advantages over other methods

The MDR1 gene defect can be detected, using molecular genetic testing techniques. By DNA testing the mutation can be shown directly. The testing is carried out by state of the art laboratory methods and therefore provides a very high accuracy. In general DNA tests can be done at any age. These tests identify both affected and carrier animals. The mutation can be shown directly, what clearly identifies homozygous affected animals. The genetic test offers the unique possibility to identify Ivermectin sensitive animals prior to treatment with Ivermectin and other drugs (see list).

* partner lab

Sample Requirements

Whole blood in EDTA tube (0.5 - 1 ml) or Buccal Swabs.

Turnaround

2 - 3 weeks

Price

£ 48.00 (including VAT)

LABOKLIN GmbH & Co. KG

ISO / DIN 17025 Accredited Laboratory

125 Northenden Road, Manchester, M33 3HF