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Concerns about MDR1

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Haven't been on the boards in quite some time, but doing some research, this thread came up, so I thought I'd bounce a few questions off you all.  I read the whole of the previous thread about MDR1, it was rather contentious at times, and I understand the emotion involved, with all parties.  That being said, initially I was not too concerned about MDR1, I like most folks always assumed Ivomec was a no no for herding/collie breeds...It was only when I found out  that  that sensitivity had a name, MDR1, which stands for "multi" drug resistance, that it wasn't only ivomec. that it was a host of other drugs as well.  I found out about MDR1 because I have a pup, that is more than likely a carrier, and possibly affected, I've not had him tested yet, but his grandsire (TG)  sire, litter mate are all carriers.  I admit to thinking that  I thought Journey (OP of the other MDR1 thread) had gone off the reservation, in what I considered over the top concern about MDR1, I'm having to rethink that now.  Full disclosure, I have a littermate to Journey's pup that is MDR1, I've had him since he was 8 weeks old, he's now just over 1 yr. old. It was shortly after he got his first vacc. I noticed there was something odd about him, I couldn't tell if it was his hearing or his eyesight...I finally settled on eyesight, I'm a photographer, so it really stuck out to me, like a sore thumb, when I would be taking pics of him, he would never look straight at me, but rather past me, even when he was playing with another dog, he wouldn't look right at them...I took him to my vet, asked her to look at his eyes, and she thought they looked fine, but said if I was concerned, I should take him to an opthm. I decided since he didn't appear to have any vision problems, I'd hold off. A couple of months ago, we started noticing that his eyes were getting kind of wonky, it was as if they were moving independently of each other (especially when he was nervous) it wasn't bad and   he displayed no other symptoms so didn't think  much of it...well fast forward to this past Thurs. took him in to be neutered (no brainer there)  I get a pm from my vet, with a vid. of Hogan, eyes going side to side, very rapid uncontrolled eye movement, or nystagmus.  He has no other symptoms, those that you would associate with vestibular issues, he appears (so far) healthy and happy...we pulled blood, it came back fine/normal, she checked his ears, clean as a whistle...running thyroid panel on him, should be back in a day or so. So that's my pup, Hogan.  Hogan also had a male litter mate, that at 6 weeks (I saw him) appeared normal, healthy, fine...at about 8 weeks ( soon after he'd received his vacc.)  when I went to pick up my pup, I didn't recognize the pup :-( OMG he had wasted away to nothing,  his head had that ferret head look to it (what you would associate with TNS) the breeder spent a fortune trying to save this pup, but to no avail. Now all along,  I had thought that surely that little dog had TNS (it's since been made known that his grandsire (TG) is also a TNS carrier. I have since been told that since the sire to my pup and the pup that died, is clear for TNS, there is no way that pup could have died of TNS, if that's the case, then would it make sense that it's possible  he died as a  result of the MDR1?  I've since heard from a woman who has a TG pup, her pup is fine, but two of the pups in the litter have had ongoing health issues, poor doers, and liver issues.  I don't know about you all, but I have grave concerns about this, and even more so, as this dog (TG)  is about one of the most widely bred dogs on the planet...I understand the ABCA is limited with what they can do, with regards to the continued breeding of this very popular stud dog, but at the very least, I feel a very strong warning should be given with regards to this MDR1 issue, I think your average puppy buyer,  is probably clueless with regards to MDR1, I know I was, and I try to stay informed about health issues on my dogs...Knowing and seeing what I've seen now, I don't think I would take a chance on   an MDR1 pup.   I think there is too much about it that we don't know...and as a person who loves Border Collies, that is very scary. 

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Mdr1 lowers the maximum dose at which adverse reactions occur  with certain classes of drugs.  These adverse reactions will stop after enough drug has been excreted by the body.  Unless that drug has damaged the body (these affect would be known for each drug) there should be no lasting effects.

 

The description you have posted does not fit with what mdr1 would cause.  TNS or Igs could lead to wasting away.  But without dna test results it is only speculation if a known genetic disease is the cause.

correlation does not prove causation 

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In the case of the pup that died, his sire was TNS and IGS clear, he (the sire) is MDR1 carrier.  So if he didn't die of TNS or IGS, then what?  Obviously you/we have no way of knowing, (although a necropsy was done)   and I understand correlation does not prove causation,  however I'm not sure how you can  definitively say MDR1 does not fit with what MDR1 would cause (in either case, the pup that died, or my pup with the nystagmus)   "Unless that drug has damaged the body..." and    "there should be no lasting effects."  I'm no scientist or doc. I shudder when I even see the word math, so I wouldn't even attempt to get into  debate with someone like yourself, but I do consider myself to have an abundance of common sense, and I think this issue warrants looking into., (as do a couple of friends of mine in the animal science field ,not Border Collie folks)  I am curious, how many dogs/pups (from this same line) cropping up showing issues as I described, and/or other health issues,  with MDR1 being the only common denominator (yikes, math term :-O )  would it take for the powers that be, to look into or take notice?   I don't plan on making a crusade of this, I really don't, it's quite clear from what I've seen, most board members seem to consider this a non issue...I think it merits notice, but I don't have the time and/or energy to go to battle over it...I'll make my thoughts known in my little sphere of influence and that's about all I can do.  I'll let you know what the thyroid panel shows on the pup with nystagmus. 

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So what drug was your pup on when it had nystagmus?

if none how could nystagmus be caused by a genetic mutation that alters how a body metabolizes and excretes certain drugs?

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He was on no drugs that I know of,  he had recently been dosed with strongid, not sure if that would cause anything...but now that I think about it, I'll have to look at timing, but there might be something to that (although it would seem unlikely) maybe not?   From the research I've been reading,  organs can be impacted by various drugs, substances, to include vaccines, (and I would think that puppies would be even more vulnerable )correct? I've seen several instances where the liver was impacted/compromised in MDR1 dogs, what I'm asking is, is it possible that, say, a thyroid could be injured as well? I'm really asking, I don't know the answer...and if something as simple as a vacc. could trigger that... From what I understand the thyroid is oft times the culprit in nystagmus.  Now I fully understand that if it is indeed his thyroid, you still couldn't link that definitively to MDR1...but you can't rule it out either...If it's not his thyroid, then I'm at a loss as to what could be going on with him... 

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Additionally, vaccination reactions are caused by immune-mediated issues, which are unrelated to the MDR1 mutation. However, clients with affected dogs may be apprehensive about giving any medications or vaccinations because of misleading information on public websites. This is a case where the veterinary technician can play an important role in preventing false information from keeping pet owners from making good treatment decisions.

 

source: https://todaysveterinarynurse.com/articles/mdr1-genetic-testing-what-you-need-to-know/

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Have you obtained the genetic test or are you relying upon relationship information to presume genetic status?  Sample quality can impact the results of genetic testing; no lab test is 100% accurate.

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The pharmacodynamics of  Pyrantel Pamoate does not involve the p-glycoprotein pathways like ivermectin.

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No, I have not had him tested yet, planning on doing it asap.  Before this episode with the nystagmus, I had not intended to test him, didn't see a reason to, as I had no intention of breeding him.  This all just happened this past Thurs.  so when the nystagmus occurred, (keep in mind, there has been something going on with his eyes since he was a pup)  then I got to thinking about the pup that died, then talking to the person who knew of 2 littermates to her pup that " have undiagnosed issues, extremely poor doers/liver issues ".  I don't consider myself a Henny Penny, but this all has def. given me pause...I'm in Texas, (where this  stud dog currently resides)  and right now I'd say you can't swing a cat without hitting a dog out of this line...I guess we'll see what turns up...I truly hope it's just all coincidental, and not related to the MDR1, I really do.  Time will tell. 

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Boop! Off the reservation :) I did not change my name to Elizabeth Warren!! 

I think it'll take enough dogs with problems for this to be taken seriously, by that time we'll be in the same boat as the Collies... 

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Mark, the link you provided above - it says the gene is dominant. How can that be?

 "Similarly, the MDR1mutation is a dominant genetic trait, so the use of the word “carrier” for heterozygous dogs is incorrect. Both heterozygous and homozygous dogs can show drug toxicosis when given P-glycoprotein substrates."

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If the mutation is dominant shouldn’t there be no differences in how the disease is manifested in mutant/mutant and mutant/normal dogs?  But the research has clearly demonstrated that disease expression in mutant/normal dogs is less and less defined (a range) than in mutant/mutant dogs.  Does that really fit the simple definition of a dominant trait?

Most people want to get a simple answer on genetics: is my dog affected or not; they don’t want to deal with the actual complex genetic consequences.  As such many writers will give what people want to hear: the simple binary answer.

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What will happen if our community decides to only breed dogs clear of every genetic disease where there is a test?

1. We breed out each genetic disease as each new test becomes available 

2. We increase the co-efficient of inbreeding of our breed (can’t breed “affected” and “carriers” of cea, TNS, igs, mdr1, EAOD, test6, test7, test8,....)

3. We increase the risk of exposing a new genetic disease for which we can develop a genetic test (test9, test10, test11, .....)

 

So do we set ourselves on the path towards what the collie is (higher level of inbreeding) by breeding out ever known genetic disease, choose to breed out selected genetic diseases (what criteria will be used to choose which diseases), or do we approach the increasing problem of more and more identified genetic diseases another way (breed for genetic diversity)?

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No. Not at all. In all other recessives there is *no* manifestation with only one copy of the bad gene. In this situation there is manifestation, to varying degrees. What I don't understand is your desire to change everything that is out there and disagree with everyone who's published, by not calling this dominant. It's not recessive.

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Go read the published articles in peer reviewed scientific literature (not lay person summaries) and there you’ll find they don’t talk dominant.

Do you want scientifically accurate information and try to gain a better understanding of it or do you want it “dumb it down”

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Ive learned a lot from these two discussions about MDR1 so thank you all. I am a dummy so most went over my head but I am interested to see where this goes.

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PaleRanger...it's a foregone conclusion where this will go...right out the window and into the breeze. I just hope that all of us dummies have enough sense to either ask, test, or refuse an MRD1 affected pup. So far though, that's just not happening. 

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IMO you and the other main contributors sounded extremely knowledgeable. I personally adopt resues or unwanted BCs because my first(which my uncle gifted me) saved my life after returning from Afghanistan so breeding isn't something I do or know much about. I do support those who work these dogs like they were bred, leading me to lean towards possibly culling while still containable. My opinion means little though, and outside this comment, will leave these decisions to the experts and hope for the best. It is good to see that people do care

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