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Juvenile Kidney Disease in UK Boxers; first update
(London & Home Counties Boxer Club Newsletter, February 2013 )
Bruce Cattanach


A year ago I wrote a brief report for this newsletter on Boxer Juvenile Kidney Disease.  This presented a basic summary of the effects of the disease and the findings indicating that JKD was inherited.  I also listed the actions I had taken.  Unfortunately, the reality of the inheritance was not accepted by all and there has since been much misunderstanding, misdirection, confusion and political turmoil.  In this update I focus exclusively on the scientific developments and findings made over the year, but I should emphasise that I have no remit from the breed to take any action whatsoever and I have no official support; my motivation has been only to help those breeders who had been hit with the problem and who had asked for my help, and they in turn have helped me.
Because of the above difficulties there was little scope for attempting genetic analyses.  Instead I pushed for a screen to find the gene responsible.  Michel Georges, who works in a Belgian lab, had a molecular method suitable for small numbers of animals, and he agreed to help.  Unfortunately his system did not detect the gene.  However, another researcher, Professor Robert Harvey from London offered to take on the search using a different methodology.  His first results were exciting.  With the use of DNA markers (SNPs) he quickly found a region where the gene might lie, and within this region there was indeed a gene that functioned in the kidney.  But subsequent investigation of the gene failed to detect a mutation within it.  This did not totally rule out the gene as a candidate for the disease, and it certainly did not rule out the region as other candidate genes are located there.  But, Professor Harvey has shifted his approach to a very different method.  This involves screening for a protein that is present in normal kidneys but is absent, or abnormal, in JKD kidneys.  From here he can work back to the gene involved, so identifying it.
There are two problems with this approach.  First, most owners are reluctant to donate kidneys from their dogs, even at post mortem.  But Boxer people have rallied.  One set of kidneys has already been provided and another two should be available within the next few weeks.  Control kidneys from normal healthy dogs are now needed.  We do have one, but we do need others to match the cases collected. 
The other problem is funding, as the new techniques are very costly.  But again Boxer people have rallied, and funding to the tune of almost £6000 has been donated and this has allowed the new research to start.
Independently of this, I have been endeavouring to collect as much information as possible about the disease and its inheritance, and for this purpose I would still like to obtain details of all possible new cases.  As of now, a single recessive gene mode of inheritance continues to be indicated but the genetic ‘penetrance’ appears very low, suggesting that many genetically-affected dogs do not develop the disease - the incidence of affected dogs appears to be well below that expected. Alternative or additional explanations for the shortage of cases are pre and early post-natal loss (low litter size, fading puppy) or that there is a different type of effect in older animals (eg kidney cancer rather than simply kidney failure).  And we have some evidence that both events are occurring.  Then another possibility is that because kidneys do a lot more than just filter urine, a range of seemingly unrelated defects may also be occurring but be attributed to other causes.  As well as this, there is a 10 fold higher incidence of primary JKD in females than in males.  JKD is complicated.  I hope this will not make detection of the gene more difficult.

Prof Harvey tells me that he does not want more blood samples or swabs.  It appears that I have flooded him with material from cases, parents and controls to the extent that he does not have enough funds to use it all, but all will be used eventually to test any gene found.  For the latter purpose I am now collecting swabs from American and Continental Boxers that have developed kidney disease so that if we find the gene in our UK dogs, we can test Boxers from around the world and establish if the same gene is responsible.  For the moment, however, the most important requirements for the research are kidneys from post mortems on affected dogs and moderately-old normal Boxers of suitable pedigree.

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