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CANINE CYCLIC NEUTROPENIA

DESCRIPTION Canine Cyclic Neutropenia is a stem cell disorder that occurs in collies. Puppies are usually smaller and weaker than their litter mates and by 8 to 12 weeks of age they develop clinical signs such as fever, diarrhea, joint pain, or other signs associated with eye, respiratory, or skin infections. The disorder is caused by an abnormality of the stem cells in the bone marrow, from which all blood cells are developed. The result is a cyclic fluctuation in blood cell numbers. Every 10 to 12 days the number of neutrophils drops dramatically, and then rebounds.

There is an increased susceptibility to infection corresponding to the dip in neutrophil numbers. Affected dogs are subject to severe recurring bacterial infections, primarily of the respiratory or gastrointestinal tract. These dogs are also prone to bleeding episodes due to the drop in blood cells numbers. This is a serious genetic disorder. Even with the best of care, affected dogs rarely live beyond 2 or 3 years of age. Most die within the first few weeks.

The disease occurs in all gray (not merle) collies. Affected puppies have a silver gray hair coat that ranges in color from very light, to darkish pewter gray, sometimes with a slight yellowing due to a mixture of light beige and light gray hair. No matter what color variation or type, all Collies have black noses EXCEPT those with gray collie syndrome. If the nose continues to come in gray, then that is pathognomonic (absolutely diagnostic) for "gray collie syndrome". Sable "gray collie syndrome" dogs have brown or pale sable noses, but never black noses as they should have.

You will be able to pick out the one dark gray puppy in this litter (tri color) , as well as the lighter gray (blue merle) . The darker appears to be a Tri-colored Gray Collie. She is a different hue from the rest of the babies. As you can see, this can usually be identified at birth. The tri  puppy died shortly after birth.

Here you can pick out the abnormal Gray puppy (blue merle) , even though there are several Blue Merles with it. Notice the "gray" has a very light, almost white sheen to her,  and her spots are dark gray rather than black like her littermates.

 She is also half the size of her littermates.

Above is the same puppy in the previous pictures,  shown at 6 1/2 weeks. She is now in a research program at the University of Washington, Seattle. 

 

photos by Dr. William Osborne

Same puppy (Sugar) at 3 months old. 

Note from Dr. William Osborne:

Sugar is currently being treated with recombinant canine G-CSF to determine her production of neutrophils in response to this hormone.  When we have established a dose-response relationship to the G-CSF we will administer intramuscularly a lentivirus encoding canine G-CSF gene to deliver life-long therapy.  We have treated two grey collies with single administrations of G-CSF-lentivirus and they both were cured of their recurrent neutropenia and remained healthy for over 18 months.

 

photos by Dr. William Osborne

Sugar at 8 months old. 

Note from Dr. William Osborne:

We completed the dose escalation of recombinant G-CSF and obtained a nice response. She is doing extremely well!  She now weighs 30 lb and received lentivirus last Tuesday.  Her WBC counts are now up to 50,000 cells/ul. This response to treatment is beyond anything we have observed before.

 

Photos by Cheryl Adlers

Sugar at 16 months old.

Note from Dr. Osborne:

Slide 1  

Sugars average cell counts before treatment, when she was cycling, were 2,090 cells/Ál.  After virus administration her average cell counts are 26,000 cells/Ál.  As you can see (per Slide 1) she has an abundance of neutrophils and this would account for her being free of infections and fever. 

 

Sugar came back home on May 23rd, 08.  She turned 3 years old on May 25th.  The photos above were taken on May 24th.  We will put up more information about her treatment when we receive it.  Although she doesn't need any special care and is now cured.

 

These photos were taken June 29th.  Sugar is such a sweet girl.  She is 33lbs and 20" tall at the withers.

Sugar, January 11th, 2009 ( 3 1/2 years old)

 

Sugar at 4 years old!

Sugar passed away at just 2 months under 5 years old of liver cancer.

A sure sign of GCS is lack of pigment on the nose.  A gray collie will have a gray or brown nose rather than black. "Gray Collies" will also lack tan markings on the face and body but this can also happen in the "white merle".  A normal Blue Merle or Tri will have typical tan markings on the face.

A sable will be almost completely white.  Above is a photo of an 8 week old sable merle "gray". 

Questions?

If you have a carrier, your dog will be perfectly healthy in every respect and you should not fear for him. BUT if you bred to another dog that carries this same gene, you not only run the risk of producing an Affected Gray puppy, you will be sure to produce other carriers.

Visit HealthGene and get the whole story on the mode of inheritance and the testing that they offer.

HEALTHGENE WEB SITE

Here are a couple of links for other collie related health problems and testing that can be done. MDR1 Drug Sensitivities in Collies DNA tests and Optigen CEA test for Non-Carriers of Collie Eye Anomaly.  HealthGene is working on a DNA marker for Epilepsy now. We will  keep going until we get PRA next.

We now have another tool to use when planning our breedings. GCS is not long gone as many breeders think it is. It's alive and kicking butt in many of today's major breeding kennels. Where did it come from? It came from everywhere in the beginning. Many breeders had to test breed and eliminate the known producers while they continued to use siblings that were carriers without even knowing it.

 

Are they at fault? No, They did the best with what they had, but they had no test and they only had half the information on the mode of inheritance. We are living in a different age now. We have DNA markers that tell us exactly where we stand with our breeding dogs. Useful information that will take us even further that we ever thought possible in the continued battle against genetic problems. What can we do now? We can test and going forward, clear our lines of this lethal gene.

Does this mean that no carrier should ever be bred? No, that's not what we are saying. There are many magnificent show dogs that excel in qualities that signify what a Collie Should be. We can't limit the gene pool from these great dogs. What we can do is take a non-carrier to this dog, select the resulting get carefully and test the ones that carry on those virtues. You can then use the non-carriers back into the breeding program. All those not kept should be spayed/neutered and placed in good companion homes. Remember, the carriers themselves are perfectly healthy.

However; with the beginnings of a non-carrier data base, we should be able to find similar dogs that do not carry this gene and just be done with it. As for me personally, I've spent over a thousand dollars testing all my breeding dogs and I'll never again breed to a carrier. As long as I am careful in my selection of partners, breeding non-carriers only, signified by the DNA status, I should never have to test again. I would rather spend the money once and start with cleared breeding dogs, than to continue to worry about this generation after generation. All our puppies and adults offered for breeding are from DNA-non carrier dogs.

 

Here is another web page that offers information regarding drug sensitivities Veterinary Clinical Pharmacology Laboratory

 

(written by Peggy Melton and Michelle Tennis)