Health | Australian Shepherd: MDR1 mutation and joint health

Santé | Berger Australien : mutation MDR1 et santé articulaire

 

Australian Shepherd: MDR1 Mutation and Joint Health

 

Sources: FCI Australian Shepherd breed standard (Group 1), Centrale Canine (LOF statistics 2024, published 2025), Firdova et al. 2016 (PMID 27234542), Gramer et al. 2011 (PMID 20655253), Mealey and Meurs 2008 (PMID 18795852), Weissl et al. 2012 (PMID 22182230), Parker et al. 2007 (PMID 17916641) and Lowe et al. 2003 (PMID 12809679).

 

 

 

The Australian Shepherd has been one of the most registered breeds in the LOF in France for several years (a position it still held in 2024 according to Centrale Canine figures).

Its energy, intelligence, and versatility have made it the preferred dog for active families and canine sport enthusiasts. This rapid popularity has also led to less favorable effects: high demand, not always rigorous breeding, and owners sometimes insufficiently informed about the biological specificities of this breed.

Two points deserve particular attention from a joint and medicinal health perspective.

First, the MDR1 mutation (also called ABCB1-1Delta), which affects a significant proportion of Australian Shepherds and alters their response to certain drugs commonly used in veterinary medicine.

Second, the joint vigilance this very active breed requires, especially in the presence of dysplasia, overweight, or unsuitable training in young dogs.

 

The MDR1 / ABCB1 Mutation: Mechanism and Prevalence

P-glycoprotein and its role

The MDR1 gene (now designated ABCB1 in official nomenclature) codes for P-glycoprotein, a transmembrane protein that functions as an efflux pump. Its role is to limit the entry of certain substances into cells, particularly at the blood-brain barrier, intestine, liver, and kidneys.

In dogs carrying the mutation, a 4 base-pair deletion in the ABCB1 gene causes a frameshift and the production of a truncated, non-functional protein. In the absence of functional P-glycoprotein, certain drugs enter the brain at much higher concentrations than normal, causing toxic neurological effects at doses usually tolerated.

Prevalence in the European population

A study published in Research in Veterinary Science (Firdova et al., 2016, PMID 27234542) genotyped 4,729 predisposed dogs in several European countries between 2012 and 2014. In the Australian Shepherd, the allelic frequency of the mutation was 35%. This high frequency translates into a significant proportion of dogs being either heterozygous (carrying a single mutated allele, less severely affected) or homozygous (carrying both mutated alleles, most at risk).

A study by Gramer et al. (Veterinary Journal 2011, PMID 20655253) confirms the significant presence of this mutation in the Australian Shepherd population in Germany and several other European countries. Mealey and Meurs (JAVMA 2008, PMID 18795852) also established the distribution of the mutation in several breeds, confirming the overrepresentation in the Australian Shepherd.

Homozygous dogs show the most severe effects. Heterozygotes can also be affected, with less marked but documented effects for certain molecules.

 

Concerned drugs

Molecule Common use Risk in MDR1 carrier

Ivermectin

(high dose)

Demodectic mange treatment Severe neurotoxicity, possible coma

Milbemycin

selamectin

Antiparasitics High risk at high doses
Loperamide Antidiarrheal Possible neurological effects

Vincristine

doxorubicin

Chemotherapy Increased toxicity
Acepromazine butorphanol Sedation / anesthesia Deeper and prolonged sedation

 

Important note: Standard doses used for parasite prevention (including ivermectin in common antiparasitics) are generally tolerated even by dogs carrying the mutation. The risk mainly concerns high therapeutic doses, such as those used to treat demodectic mange.

 

Genetic testing

An ABCB1 genetic test is available from several veterinary laboratories in France and Europe. It determines whether a dog is homozygous wild-type, heterozygous, or homozygous mutant.

This test is particularly recommended before any chemotherapy, before using high doses of antiparasitics, or before anesthesia involving concerned sedatives. The result should be included in the dog's health record and communicated to any new veterinarian.

 

Joint Health: Dysplasia, Growth, and Activity Management

Hip and elbow dysplasia

The Australian Shepherd is among the breeds for which hip and elbow dysplasia is a recognized orthopedic concern. These two pathologies have both genetic and environmental components. The OFA database lists significant rates of dysplasia in the tested population, although figures vary depending on populations and screening protocols.

Dysplasia frequently progresses to secondary osteoarthritis. In the Australian Shepherd, environmental factors (inappropriate exercise at a young age, overweight) can exacerbate pre-existing joint fragility and accelerate this progression. Repeated mechanical stresses in a very active dog can worsen pre-existing joint fragility, especially in the presence of dysplasia, but they do not in themselves constitute a demonstrated cause of osteoarthritis specific to the breed.

Puppy management: common mistakes

Skeletal maturity is only reached between 12 and 18 months. Before this age, cartilaginous surfaces and growth plates are vulnerable to significant mechanical stress.

Avoid before 12-15 months: prolonged jogging, repeated jumping, high-impact exercises on hard surfaces.

Monitor: weight gain during the growth phase: juvenile overweight increases joint risk.

 

Other documented health points

Idiopathic epilepsy

The Australian Shepherd is one of the breeds predisposed to idiopathic epilepsy. Knowledge of the dog's MDR1 status can be relevant in the choice and dosage of antiepileptic drugs used (an element documented by Weissl et al. (JVIM 2012, PMID 22182230) in this breed).

 

Collie Eye Anomaly (CEA)

Collie Eye Anomaly (CEA), affecting the development of several ocular structures, is the best-documented eye pathology in this breed. The NHEJ1 gene mutation has been identified in several studies (Parker et al. 2007, PMID 17916641; Lowe et al. 2003, PMID 12809679). A DNA test is available.

 

Double merle

Merle-colored Australian Shepherds carry the merle gene (M), which randomly dilutes pigmentation. A dog carrying two copies of this gene (homozygous MM, known as "double merle") has a very high risk of partial or total deafness, microphthalmia, or blindness. Mating two merle dogs is contrary to animal welfare and is discouraged by veterinary organizations and serious breed clubs.

 

What to check before adopting an Australian Shepherd

MDR1 test: ask for the ABCB1 genetic status of the puppy and its parents (a serious breeder will systematically provide this).

Parental joint health assessment: hip and elbow X-rays of the breeding dogs, to be requested before purchase.

Ocular assessment: CEA test available (to be checked in parents).

Merle x merle: never acquire the product of a merle x merle mating (major risk of malformations).

Activity level and growth: this breed has high needs, which must be adapted to the dog's age and orthopedic condition. Do not over-exercise before 15 months.

 

 

Is your Australian Shepherd concerned?

MDR1 mutation, joint problems, veterinary follow-up: if you live with an Australian Shepherd and wish to share your experience, your testimony can help other owners.

Write to Canithermo:

contact@canithermo.com


Sources 

  1. FCI Australian Shepherd breed standard (Group 1)
  2. Centrale Canine (LOF statistics 2024, published 2025)
  3. Firdova et al. 2016 (PMID 27234542)
  4. Gramer et al. 2011 (PMID 20655253)
  5. Mealey and Meurs 2008 (PMID 18795852)
  6. Weissl et al. 2012 (PMID 22182230)
  7. Parker et al. 2007 (PMID 17916641)
  8. Lowe et al. 2003 (PMID 12809679).


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