UPDATE as of 11/15/06: From Katy Robertson at UC Davis, where the test is performed:
"We have tested 362 Border Collies (not controlled for relatedness) to date and have seen the MDR1 mutation in only 1 dog. This dog was a rescue with unknown pedigree; therefore, we didn't include the dog in our findings."
Based on the above information, this drug sensitivity gene has not yet been found in purebred border collies in this country. Since the mutated MDR1 gene is fairly common in many breeds that can look like border collies, dogs with unknown pedigrees should not be counted as border collies. However, some testing institutions log in breed data based solely on the owner's description of the breed. The ABCA Health and Genetics Committee will continue to follow the verified statistics of this mutation in purebred border collies.
12/12/07 Katy Robertson at UCDavis reports no pure bred Border Collies found with the mutation; the number of tests being run has decreased and few additional Border Collies have been tested. (edited by Mark Billadeau)
I have pulled from the Boards posts to help clarify the issues with heartworm preventative sensitivity and links to websites with additional information.
Here's a little more detail on Denise's point #2.
Important points to remember
1) The normal dose of ivermectin used for prevention of heartworm in products such as Heartguard (6 micrograms/kg) is not documented to cause the toxicity associated with this mrd1 mutation in collies or any other dog. It is only when higher doses are used, often by people mistakenly thinking the cattle/sheep dose is appropriate for dogs, that toxic symptoms appear in susceptible dogs.
2) Any of the avermectins, the class of chemicals ivermectin belongs to, are capable of producing the same toxicity in affected dogs when used at high doses. The commonly held belief that heartworm preventives such as Interceptor are safer than Heartguard is incorrect. Both products are safe at the low dose used. However, there are confirmed reports that moxidectin, which is used in the six month injectable for heartworm prevention, has caused neurotoxicosis in susceptible collies.
3) Any breed of dog can suffer from toxicity and death from ivermectin and the related class of drugs if they consume high enough levels to penetrate the blood-brain barrier. Levels of ivermectin shown to cause toxicity in beagles, a breed that does not have the mdr1 mutation are 2.5 - 40 mg/kg which is greater than 200 times the therapeutic dose.
Special considerations for farm dogs
An important consideration not everyone is aware of is that farm dogs often consume ivermectin or other avermectins in the manure from recently treated stock. Merck reports an apparent half-life for ivermectin of 1-1.5 weeks in sheep manure from sheep wormed with the standard drench dose of 200 micrograms/kg. They also estimate typical soil incorporation rates for manure from treated sheep to range from 0.16 ppb to 5.1 ppb. (From http://www.fda.gov/c...31-392FONSI.pdf ) Therefore, it?s possible for collies and other breeds known to have the mdr1 mutation to consume a toxic dose of ivermectin from eating the manure of recently wormed stock. The timing of worming stock with avermectins should also be taken into account when giving farm dogs heartworm preventative to prevent accidental overdose.
Partial list of drugs known or suspected to cause problems in dogs with the mdr-1 mutation
Ivermectin (antiparasitic agent)
Loperamide (Imodium?; over-the-counter antidiarrheal agent)
Doxorubicin (anticancer agent)
Vincristine (anticancer agent)
Vinblastine (anticancer agent)
Cyclosporin A (immunosuppressive agent)
Digoxin (heart drug)
Butorphanol (pain control)
Partial list of drugs thought to have the potential to cause problems with the mdr-1 mutation
Reference: Neff, et al, 2004
As far as the internet reports on cases of ivermectin sensitivity in border collies, as I said, I contacted the people who do the gene test and they said no border collies had been confirmed to have the mutation. I asked specifically about the unconfirmed reports and they are still unconfirmed. The number of border collies that've had the test is now over 300.
C Denise Wall, PhD
Washington State University Multidrug Sensitivity Study
So-called "ivermectin" sensitivity is actually sensitivity to a broad class of compounds due to a basic defect in the blood-brain barrier. Normal dogs are protected from acute and often fatal neurotoxicoses when these compounds are administered as pharmaceuticals (including ivermectin) by P-glycoprotein, an ATP-dependent drug transporter that moves a broad spectrum of substrates across several tissue borders throughout the body. The normal gene encoding for P-glycoprotein is MDR1.
Anti-helminthic pharameuticals that are P-glycoprotein substrates include the family of compounds known as macrocyclic lactones. These compounds exert their anti-helminthic properties by causing neurotoxicosis in a number of invertebrates (including helminths and arthropods) by potentiating ligand-gated chloride ion channels in the peripheral nervous system. Generations of macrocyclic lactones known as avermectins have been developed for veterinary use, decreasing their toxic side effects to normal animals (without the mdr1-1Δ mutation).
These compounds include: ivermectin (HeartGard), milbemycin oxime (Interceptor and Sentinel), moxidectin (Proheart), selamectin (Revolution), and doramectin (Decomax).
Given the mechanism for toxcity, there is no reason to consider milbemycin oxime safer for dogs with the mdr1-1Δ mutation than ivermectin. The monthly oral dose of both ivermectin and milbemycin oxime has been administered for heartworm prophylaxis to Collies homozygous for mdr1-1Δ without incident and both have been shown to have similar pharmaceutical margins of safety in sensitive Collies (Tranquilli et al. 1991). (source American Working Collie Association)
Testing your dog for the mutation
The Bottom Line:
Based upon current information, all of the monthly heartworm preventatives are equally effective and equally safe.
[ 11-16-2006, 10:01 AM: Message edited by: Eileen Stein ]