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MDR1 - can we eradicate?


Journey
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Ivermectin is no more risky than the other macrocyclic lactones and it has been known for decades the dose at which mdr1 m/m (I.e. sensitive collies) dogs show adverse reactions. That info has always been on the product inserts for heartgard.

 

Btw, the Merck Vet Manual lists the recommended dose of ivermectin for deworming dogs AND it falls within the WSU SAFE dose range for mdr1 m/m dogs (6ug/kg).

 

A better analogy is a drug allergy; prescribed treatments need to work within narrower limits set by the genetic mutation.

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If carriers of a recessive gene are unaffected then the gene pool size argument is a valid one imo. Testing, and carefull breeding can manage.

But if, as Journey her argues, heterozygote carriers of this particular gene can be seriously affected, then responsible breeding means doing everything to eradicate it.

And that means not breeding carriers.

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If carriers of a recessive gene are unaffected then the gene pool size argument is a valid one imo. Testing, and carefull breeding can manage.

But if, as Journey her argues, heterozygote carriers of this particular gene can be seriously affected, then responsible breeding means doing everything to eradicate it.

And that means not breeding carriers.

 

Smalahundur makes a good point. Doesn't it make more sense to eliminate affected carriers now when the incidence in border collies is low rather than to wait until it becomes more widespread? How many breeding dogs would be removed from the gene pool now as opposed to waiting until there are many more dogs to present a threat?

 

Does anyone have even an approximation of the current incidence of heterozygous "carriers" in border collies? I get that it will be higher than the <0.5% of affected (m/m), but is it possible to extrapolate? It seems to me that it would still be a pretty low incidence.

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For heaven's sake. Sorry, been away, I just discovered this thread.

This is the HEF site that I assume Journey is talking about:

https://bordercolliefoundation.org/health-and-eduction/genetic-diseases/

If everyone referred to that -- the chart, and the info on MDR1 (ABCB1) in the text below it -- it would make the issue clearer.

The chart used to say "recessive" as the mode of inheritance. Following contact from Journey and a review of the literature, we dropped that, and substituted a description of the implications of heterozygosity and homozygosity in the text. We do not feel we can use the term "affected" to describe heterozygous dogs for the reason Mark states -- "Affected" is commonly understood to mean homozygous mutant.

It took us awhile to agree on the best language to use, but the wording there now has been up for quite a while -- more than a month anyway. The only wording still under discussion is the prevalence rate, which we hope to have resolved soon.

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We periodically read about how dogs can die from eating ivermectin laced manure. So how much manure does a 40lb MDR1 m/m dog need to eat?

 

WSU lists MDR1 m/m dogs have adverse reactions at 0.14-0.27mg/lb (5.6mg-10.mg for a 40lb dog).

 

Ivermectin dose for sheep is 2.4mg/26lbs (9.2mg for 100lbs).

 

The half life of ivermectin in sheep is 1-2days and >90% of the drug is excreted in manure.

 

All of the above can be found in published scientific articles. What follows are estimates.

 

Nutient management programs use this estimate: 100lb sheep produces 4lbs manure daily.

 

The density of manure is less than that of water, but I will use the density of water as a worst case value.

 

A 100lb sheep will excrete 4.8mg ivermectin in 4lbs manure within the first day after drenching.

 

The 40lb MDR1 m/m dog will need to consume 4.7-9lbs of laced manure to get enough ivermectin to have an adverse reaction; or 9-17 cups of manure.

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Thanks for hat Mark. It was a question I have been asking myself; whether it was likely that an affected dog could have dangerous reactions to medication ingested this. I always found it hard to believe, but didn't have the numbers. Looks like it is pretty unlikely.

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We periodically read about how dogs can die from eating ivermectin laced manure. So how much manure does a 40lb MDR1 m/m dog need to eat?

 

WSU lists MDR1 m/m dogs have adverse reactions at 0.14-0.27mg/lb (5.6mg-10.mg for a 40lb dog).

 

Ivermectin dose for sheep is 2.4mg/26lbs (9.2mg for 100lbs).

 

The half life of ivermectin in sheep is 1-2days and >90% of the drug is excreted in manure.

 

All of the above can be found in published scientific articles. What follows are estimates.

 

Nutient management programs use this estimate: 100lb sheep produces 4lbs manure daily.

 

The density of manure is less than that of water, but I will use the density of water as a worst case value.

 

A 100lb sheep will excrete 4.8mg ivermectin in 4lbs manure within the first day after drenching.

 

The 40lb MDR1 m/m dog will need to consume 4.7-9lbs of laced manure to get enough ivermectin to have an adverse reaction; or 9-17 cups of manure.

In light of all of that, what are your thoughts on this story?

 

http://now.tufts.edu/news-releases/dog-s-recovery-tufts-highlights-need-genetic-testing-owner-vigilance

 

I mean, Ive never really been bothered by the MDR1 gene in light of how much a dog would need to ingest. But then I read that story and Im wondering if there are more factors involved in how it affects a dog?

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That article makes no mention of how the dog may have been exposed to ivermectin; only that tufts warns about the amount of ivermectin in horse wormers.

 

Have you ever read the product inserts for ant baits?

 

Mdr1 n/n dogs can get ivermectin toxicosis

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If only it was JUST ivermectin....

 

Anyway, with the Mdr1 defect having a different expression then the other defects that we currently have testing for with the odds of having more tests developed in the future that would likely have similar expression, seems that this would be the best time to start educating breeders on more then simple recessive defects so that they can make better decisions in the future as more tests are developed. I recall the same confusion when the test was released for HYPP in quarter horses, people didn't understand that N/n's would also be prone to exhibiting the defect only understanding simple recessive.

 

Seems that this falls into the "Education" category and should be looked as a opportunity to better educate for the future, unless DNA testing as we know it is some how going to debunked and fall off to the wayside as a means of defect testing.

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Duly read. Is the HEF going to give a recommendation on breeding m/n and affected dogs?

 

Ivermictin has been the thrust of this topic, what about the cancer drugs and the anesthesia drugs? No problem? Just carry on as has been and no big deal?

 

If it's really a non issue should we even test for it?

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Doesn't matter to me at all. I've no dog in this fight. I'm asking if the website is going to stay consistent, or is this the exception? Is the exception due to "who" it involves?

 

You've gone out of your way to say how horrible ivermic is in general, ok, so will the site reflect that this is no big deal, stay below the radar so to speak? Until we get to a point like the Aussies or Rough Collies?

 

ABCA doesn't ban breeding, only makes recommendations, yet it's lacking here. Why's that? What I want is no big deal, a healthy breed. Is healthy relative to whom it involves?

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Journey, I'm not sure I understood your last post correctly.

 

First off, you've apparently read the MDR1 material on the HEF website. Can you please tell me if there is anything there that you believe to be incorrect? Or is your issue only that it contains no breeding recommendation?

 

Second, you seem to be suggesting here that HEF is misrepresenting or suppressing something about MDR1 due to "who it involves." Am I reading you right? If so, would you please be more specific about your allegation? Who is it that you believe HEF is trying to favor, appease, help, or whatever by what we are doing or failing to do? Why would we want to favor, appease, help, etc. this person?

 

Third, I think you have misunderstood Mark's posts about ivermectin. I did not read them as saying ivermectin is horrible.

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When drugs are developed the minimum effective dose and maximum safe dose are determined using mdr1 n/n dogs. For dogs that have one or two of the mutant mdr1 genes the maximum safe dose is lower for the problem drugs. Its not that the problem drugs are no longer usable.

 

These lower maximum safe doses are listed on the WSU website.

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