Cyclic Neutropenia

Other Names: Cyclic hematopoiesis, Gray collie syndrome, CH, CN
Affected Genes: AP3B1
Inheritance: Autosomal Recessive
Mutation: chr3:28663129-28663130 (canFam3): 1 bp insertion (ins A)
Breed(s): Collie, Old-Time Scotch Collie, Rough Collie, Scottish Collie, Smooth Collie

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Common Symptoms

Cyclic neutropenia is an inherited disease affecting collies. Affected dogs undergo an oscillating cycle in the quantity of a type of white blood cells called neutrophils, important for controlling and preventing bacterial and fungal infections. Affected dogs have Neutrophil counts oscillating between normal quantities to almost zero neutrophils on an approximately 2 week frequency. Affected puppies often die within a few days of birth or are stunted in growth. Affected dogs have a gray coat color and are vulnerable to infections during periods of low neutrophil counts. Symptoms associated with this condition are normally seen during or immediately after a period of low neutrophil counts. Symptoms include fever, diarrhea, inflamed lymph nodes, gingivitis, lameness and mild bleeding episodes. Even with medical care, most dogs die before 2 years of age due to liver or kidney failure.

Testing Tips

Genetic testing of the AP3B1 gene will reliably determine whether a dog is a genetic Carrier of cyclic neutropenia. Cyclic neutropenia is inherited in an Autosomal Recessive manner in collies meaning that they must receive two copies of the mutated gene (one from each parent) to develop the disease. In general, carrier dogs do not have features of the disease but when bred with another carrier of the same Mutation, there is a risk of having affected pups. Each pup that is born to this pairing has a 25% chance of inheriting the disease and a 50% chance of inheriting one copy and being a carrier of the AP3B1 gene mutation. Reliable genetic testing is important for determining breeding practices. In order to eliminate this mutation from breeding lines and to avoid the potential of producing affected pups, breeding of known carriers to each other is not recommended. Dogs that are not carriers of the mutation have no increased risk of having affected pups.

There may be other causes of this condition in dogs and a normal result does not exclude a different mutation in this gene or any other gene that may result in a similar genetic disease or trait.


  • Benson KF, Li FQ, Person RE, Albani D, Duan Z, Wechsler, Meade-White K, Williams K, Acland GM, Niemeyer G, Lothrop CD, Horwitz M. Mutations associated with neutropenia in dogs and humans disrupt intracellular transport of neutrophil elastase. Nat Genet. 2003 Sep;35(1):90-6. [PubMed: 12897784]
  • Lothrop CD Jr, Coulson PA, Nolan HL, Cole B, Jones JB, Sanders WL. Cyclic hormonogenesis in gray collie dogs: interactions of hematopoietic and endocrine systems. Endocrinology. 1987 Mar;120(3):1027-32. [PubMed: 3026784]