Friday, March 16, 2012

Boxer JKD from My Side ~ Dr Bruce M Cattanach, Steynmere Boxers, UK

Since the recent PDE TV programme (27th February), comments on the content have been presented from all sides in the UK dog press and online – all except mine that is – and as one of the participants in the Boxer Juvenile Kidney Disease section of the film, and as I have since been the subject of some outrageous charges, I think it appropriate that I give “my side” of Boxer JKD.

Unfortunately, because the shocking developments at Crufts have dominated the news reported by the UK dog press, I can't give my response in the same media this week and maybe not for several weeks, so here I offer my story as it actually happened: 

I have for years monitored cases of kidney failure in UK Boxers and have seen no indication of it being inherited.  Therefore, when the subject was raised at a Breed Council Health Committee meeting a few years ago, I expressed little interest, although another member of the committee was eager to investigate.  

However, in late September 2010, I received a call from a vet seeking help for a client, Ms Sharon McCurdy, who had a number of cases of JKD and had failed to get any help from her previous vet. I was initially rather skeptical and took the news rather lightly, but a subsequent letter threatening me with legal action, received after I responded to Ms McCurdy’s vet but before I had any idea what was going on, did get my attention.

Examination of Sharon McCurdy's and further cases that quickly came to light revealed an extraordinary picture of litters with one or more kidney deaths occurring with very close inbreeding (father x daughter, half-brother x half-sister, g’father x g'daughter, etc, focusing on one dog).  But as more cases were found, some revealed close inbreeding on dogs that were further back in the first pedigrees.  There was therefore clear evidence of an inheritance that nobody could miss.  The close inbreeding suggested a recessive gene inheritance.  But there were also a few cases that derived from total outcrosses.  This meant either that they had a different causal basis (poisons, etc) or that the gene responsible was more widely spread than yet recognized.

Professor Bell, a specialist in Internal Medicine at Glasgow University Veterinary School, agreed to help devise a questionnaire on which the vets could enter their diagnostic evidence.  Retrospectively this was achieved for almost all cases. The cause of these deaths can therefore be ascribed to a juvenile kidney disease (JKD).  One of these familial cases died in Sweden and went to a full post mortem to get the more specific diagnosis of familial renal dysplasia. 

I reported the findings in Boxer Breed Notes as the cases emerged and, on request, subsequently (February 2011) exhibited the pedigrees to the Breed Council Executive and a new Health Committee.  I presented only my general conclusions and left interpretation to those present to decide for themselves. There were no questions on the pedigrees as I recall, only questions on the diagnoses.  Because of the perceived magnitude of the problem, I offered only one recommendation for breeders – “to try and avoid inbreeding.”  Judging from a subsequent report in the dog press by the new Health Committee, everything appeared to be accepted, including my aim to initiate a study to find the responsible gene.

I was lucky enough to find an interested molecular geneticist, Michel Georges from Belgium, who was using a new gene scanning method that seemed appropriate for our situation.  Week after week thereafter, I therefore put requests in the dog press for blood samples.  I needed samples from both affected cases and parents, but the response for each was very poor.  People seemed frightened.  Two owners actually told me that the breeder had told them not to cooperate.  However, I managed with great difficulty to get 5 samples from affected cases and 6 from parents.  All offers of samples were accepted and in fact I am still looking for more.  I also needed unrelated controls and managed to get enough contributions from concerned breeders to be able to select ones I hoped would be suitable for the gene screen. The screen started but it was not successful. Other investigations elsewhere in the world with other Boxers have likewise failed.

 Coming now to the film, when Jemima Harrison informed me that she had been besieged by Boxer breeders to take up the JKD problem and asked me if I would contribute and explain the genetics, I of course agreed.  I could not possibly stand back and let other brave souls fight alone.  I therefore told her the story much as above, but eventually had to produce the evidence – the pedigrees – and I know these were then carefully analyzed by two other geneticists.  The film makers also sought out other factual information on events which made my own efforts on the genetics seem puny. Believe me, there is so much more information, but only a small part was given in the 10 minute slot in the 1 hour programme, and I know that every word was scrutinized by a team of lawyers.

I do want to make it clear that what I actually said can be literally “seen” on the film. The remainder came from the narrator, not me.  It was selective, excluding much, but still accurate in content.  I was saddened that my comment on the exceptional past record of UK Boxer breeders on health matters was not given.  And I was annoyed that the narrator made it seem that the evidence that JKD was inherited was not definitive just because the gene had not been found (a lawyer issue, I'm told).  But let's be clear.  One needs breeding evidence before one searches for a gene, not the other way around. The evidence that JKD is inherited is absolutely firm, and two other geneticists agree.

Where do we go from here?  Further research upon JKD is needed but I hope it can be seen that this would be impossible at present.  Instead we are left with the one option of separately trying again to find the gene.  Here, I thought we might still get stuck because what research group would be willing to invest much time and a huge funding to look for a gene when there is not total positive breeder support.  

However, I was delighted to receive a message after the film from Swedish canine geneticist, Ake Hedhammar, who works with American/Swedish molecular genetics guru, Kerstin Lindblad-Toh, on JKD in Continental and American Boxers.  He suggested we collaborate with him in his effort to find the gene for JKD in Boxers internationally. This could be the way to go, but would we get full support from owners of cases and parents a second time around?  I actually had 5 possible JKD cases reported in the three days following PDE2 with blood samples promised, which is quite a change. Maybe the film has actually rescued the breed.

Postscript:  I have just had another offer of help to find the gene, this time from Professor Harvey of University College London.  His interests are medical, but he has taken an interest in disease genes in dogs that may have relevance for human disease. This route seems a very promising one, as collaboration with human researchers has worked very well for me with Boxer Cardiomyopathy as I hope will soon be seen.  So, if the Boxer breed in the UK wants to get itself together, face the problem, and do something, there could be a way forward.  And please note, it to be expected that any further research will require blood samples from additional affected cases and also from their parents, so all of you out there, please help.

NEWS FLASH!!!   Dr Kerstin Lindblad-Toh of the Broad Institute at MIT, who has been collecting DNA samples for JKD in both the US and Europe for some time, has now also  expressed an interest in the UK investigations and collaborating in an extended search for the gene responsible for this fatal Boxer kidney disease!

1 comment:

  1. Virginia, thanks for publishing Dr. Cattanach's document. It contains important information that deserves wide circulation in the breed's interest!