Gray Collie Syndrome (GCS)
Gray Collie Syndrome (GCS) is a form of canine cyclic neutropenia affecting the Collie breed. Cyclic neutropenia is a form of neutropenia, a condition of abnormally low concentrations of neutrophils in the blood. It has been recognized in humans and dogs.
Neutrophils are form of white blood cells or granulocytes that are the most numerous white blood cells in mammals. Other types of granulocytes next to neutrophils are osinophils and basophils. They are produced in the bone marrow and formed from stem cells, undifferentiated biological cells. Their life span is of short durance. Neutrophils are highly mobile and they can enter parts of tissue where other cells are not able to. They are also a type of phagocytes and have an important role in defence against various types of infection. They are the first responders of inflammatory cells that migrate towards location of inflammation caused by bacterial infection, environmental exposure or some cancers.
Neutropenia is a term for low neutrophil counts. It can be hereditary or it can be developed during life, as form or aplastic anaemia or some kinds of leukaemia, but it can also be a side effect of medication such as chemotherapy. Gray Collie Syndrome is a form of neutropenia that is hereditary and it is caused by a defect in the bone marrow stem cells. It is named cyclic neutropenia due to cyclic fluctuation in blood cell numbers. GCS is characterized by a sudden fall in neutrophil levels every 10 to 12 days, after which it rebounds. With important role of neutrophils in the immune system, this sudden drop has a severe negative impact on dog’s overall health.
Affected cubs appear to be weaker and can be recognized by its greyer or light coloured fur in any colour compared to the fur of other, healthy cubs. Affected Collies will never have black nose, unlike the healthy ones whose nose is always black. Due to immunity problems caused by low neutrophil count, affected dogs suffer from gastrointestinal problems, fever, bleeding, blood poisoning and bacterial infections of the eye, respiratory system or skin. The life expectancy of Collie with cyclic neutropenia is usually less than three years.
Canine cyclic neutropenia, or Gray Collie Syndrome, is caused by a mutation in the canine AP3B1 gene. Gray Collie Syndrome is inherited as an autosomal recessive disorder. Healthy parents of an affected puppy are obligate heterozygotes, and therefore carry one mutant allele. Heterozygotes have no symptoms. Dogs homozygous for the mutation will display the symptoms of the cyclic neutropenia. At conception, when mating two carrier dogs, each cub has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier.
Benson, F. K. et al. (2004.): Paradoxical homozygous expression from heterozygotes and heterozygous expression from homozygotes as a consequence of transcriptional infidelity through a polyadenine tract in the AP3B1 gene responsible for canine cyclic neutropenia. Nucleic Acids Research, 2004, Vol. 32, No. 21 6327–6333