© Therese Rodin
Background: There are not many Pugs in the literature who are said to have developed DM and they rarely occur e.g. in Facebook groups for owners of DM afflicted dogs. However, DM is a very serious disease, as can be seen from the following quote:
”Disease progression is relentless, and dog owners often elect euthanasia within 1 year after onset of clinical signs when their dogs become paraplegic [= paralyzed in the hind legs and the lower part of the trunk]” (Zeng et al. 2014: 515).
We are concerned that the disease might increase in the Pug if more Pugs become heterozygous with the defect allele. If the breeders do not test their Pugs, in the end the heterozygous Pugs will produce puppies that are homozygous with the defect allele. The OFA statistics on DM can tell us something about the spread of the allele in the Pug. At the point when I was visiting the webpage, 557 Pugs had been tested for DM. Of these, 68 Pugs (12.2%) were homozygotes and 183 (32.9%) were heterozygotes with the defect allele (data collected 221019). The homozygotes are called “at-risk” since they have an increased risk of developing the disease. (To note is that we do not know if any of these Pugs had fallen ill in the disease.) The heterozygotes are called “carriers” since they carry the defect allele and may transmit it to their offspring but they do not have a higher risk to develop the disease. Thus, in these data the amount of homozygotes is fairly low. However, one third of the tested Pugs were carriers. As was pointed out, this group could be a potential for future homozygotes and an increase of the disease.
As we saw above, DM is a horrible disease. It develops through a fast degeneration of the spinal cord. (Contrary to PM where the spinal cord is compressed locally.) DM affects both sexes and usually occurs after the age of five, with an average age of 9 years, at least in large dogs. It has a genetic background similar to that of ALS that can affect humans. Just like ALS, DM has a fast course. Large dogs lose all ability to use their hind legs 6–9 months after the onset of disease, when they are usually euthanized. Smaller dogs affected by DM usually live longer because it is easier for the owner to give them support when they can no longer walk. In Welsh Corgi Pembroke, the median for life span after disease onset was 19 months in one study (Coates 2004).
The research on DM and the interpretation of data is complicated, and the main reason for this is that the gene that the researchers have identified as linked to the disease (a mutation of the gene for SOD1) is only part of several other underlying causes that we do not know. At first, DM was seen as a German Shepherd disease, but it has later been seen that it is found in many breeds, both large and small (Coates 2004). The Pug is listed as one of the breeds tested for DM, SOD 1, exon 2 at Laboklin. Also ofa.org (about DM) lists the Pug as one of the breeds that can be affected by DM. The Bernese Mountain Dog has been shown to have its own mutation variant on the SOD1 gene.
Just as with PDE/NME, not all at-risk (homozygous) develop the disease and there are many breeds where a large part of the population has this mutation without anyone getting sick (Beuchat 2018). Zeng et al. examined DNA from 32,378 pure-bred dogs from 22 breeds and 1,368 mixed breeds. 49% of the dogs were homozygous with the healthy allele for SOD1 called G. 27% were heterozygous with the mutated allele (G/A) and 24% were homozygous with the mutated allele (A/A). In total, 37% of the dogs had the mutated allele, both heterozygous and homozygous counted. There were 382 Pugs included in the study and of these, 47% had the defective allele (A). 30 of them were carriers (heterozygous) and 17 were at-risk (homozygous) (Zeng et al. 2010: 517, Table 1).
Zeng et al. also examined the spinal cord of 173 dogs during autopsy. Of these, 115 had been confirmed to have DM and 58 had not DM. Of the 115 DM-sick dogs, 105 were at-risk, being homozygous with the defective allele (A/A). Eight of the dogs with DM were carriers (G/A) and two of them were homozygous with the normal, healthy allele (G/G). Of the 105 homozygous with the defect allele who had fallen ill, two were Pugs. They also had a Pug that was homozygous with the defective allele but did not have DM (Zeng et al. 2010: 518). Thus, among the dogs that had the spinal cord examined, three Pugs were homozygous with the defective allele and of these two had fallen ill. Furthermore, also Jon Patterson (vet.med.dr.) who studies gait anomalies in the Pug at Michigan State University has autopsied Pugs showing signs of spinal cord DM (private communication).
Since it appeared that even heterozygous dogs that had the defective allele had some risk of developing the disease, Zeng et al. examined 137 of the healthy dogs included in the study through follow-up of clinical status. Of the dogs who were homozygous with the defective allele (A/A), 60% had developed the disease. Of the heterozygotes (G/A), 4% had developed DM and of those who only had the non-mutated gene, 6% had developed the disease. Based on this result, the researchers believe that breeders should avoid the birth of homozygotes of the defective allele, but heterozygous dogs are not seen as a major risk (Zeng et al. 2010: 520).
Goal: The goal is that no Pug will develop this disease.
Below you see Meatball, “Meaty”, who lived with his family from the age of eight weeks. Meaty got DM when he was 11 years old. The process was fast but he lived until his 12th birthday. You can read a text here written by Meaty’s dad Alex Sotelo who tells about some experiences of living with a Pug with DM.
Strategy: As we saw above, not all dogs who are homozygotes with the mutated SOD1 gene do develop the disease. Because it is so serious, we still advocate that all dogs that are intended for breeding should undergo gene testing for degenerative myelopathy. However, since both the OFA statistics and Zeng et al:s study suggest that there is a large proportion of the Pugs that have one or two defective alleles in a gene pair, too much genetic material would be lost if all of them were removed from breeding. A Pug that has the duplication of the gene should instead be combined with one that is free and the same applies to carriers. Eventually we will not have any at-risk dogs left, which means that we come as close to the breeding goal we currently can in terms of DM.
Designations of free, carriers and at-risk:
Sources and further reading:
Beuchat, Carol. 2018. ”The lesson(s) from SOD1 and degenerative myelopathy“. Blog article, Institute of Canine Biology. Accessed 220119.
Coates, Joan R. 2004. ”Canine Degenerative Myelopathy”. BSAVA, 394–407.
Patterson, Jon. Email from 100918.
Zeng, R. et al. 2014. ”Breed Distribution of SOD1 Alleles Previously Associated with Canine Degenerative Myelopathy”. Journal of Veterinary Internal Medicine 28, 515–521.
Chapters in Strategies for the breeding of Healthy Pugs
- Hips, Elbows and Patella
- Hemivertebrae and other vertebral anomalies
- Spinal Arachnoid Diverticulum (SAD)
- Pug Myelopathy (PM)
- Degenerative Myelopathy (DM)
- PDE/NME and other non-viral induced encephalitides
- Brachycephalic Obstructive Airway Syndrom (BOAS)
- Dentition and mouth health in the Pug
- Eyes (Brachycephalic Ocular Syndrome)
- Mating and Fertility
- Genetic diversity