by Gina White - Zwinger Der Meer Küste
As an owner and breeder of German Shepherd Dogs for over
thirty years, I have been asked many health-related questions
regarding the breed I am so enamored by.
In the past several years, aside from hip and elbow dysplasia, the
biggest concern from GSD owners is the occurrence of
degenerative myelopathy, or DM. For those not familiar with
DM, it is a progressive degenerative spinal cord disease,
typically occurring in dogs over 8, which is characterized by
hind limb paralysis and an eventual loss of other motor
functions.
Since first described in the early 1970s, DM was understood to be a degeneration of the spinal cord due to an unknown cause. But in 2009, Dr. Joan Coates, a veterinary neurologist and associate professor of veterinary medicine and surgery in the MU College of Veterinary Medicine, and her peers, identified
the mutation in the gene superoxide dismutase 1 (SOD1) as the primary cause of DM. Mutations in SOD1 are associated with
some forms of human amyotrophic lateral sclerosis (ALS), also
known as Lou Gehrig’s disease, which is adult in onset, causing
muscle weakness and eventually respiratory failure therefore
sharing many traits of the canine expression of this mutation. Dr.
Coates begins, "The SOD1 mutation is mostly recessive (2
copies); however, some carriers in certain breeds like German
Shepherds get DM. The mutation is a risk factor with higher risk
in dogs with 2 copies."
In other words, not all dogs that have the mutation will develop
DM so the mutation test, although beneficial to breeders and
owners alike is currently a test for risk.
Dr. Coates goes on to say the SOD-1 mutation is an ancestral or
very old mutation, probably present since the first GSD, Horand
(Hektor) was registered by the SV in 1899 but so many years
later, it would be impossible to say for sure. When asked why
the disease only seems to be on the radar in recent decades she
says, "I believe the gene mutation has been present since the
breed's inception. In my opinion and I have no statistical or
empirical evidence to support it, but given that DM is a late
onset disease and dogs are living longer due to better lifestyle
and healthcare, may be one reason the 'known' incidence of
disease is increasing."
Dr. Daniel Kelleher, DVM, who practices reproductive medicine
at Broadview Veterinary Hospital in Dover, NH, also added in
his knowledge regarding DM. 'I think DM has been there all
along as well but now it's something that is actively tested for"
he states. "I think the notion of bad breeding is sort of a
misconception since breeders didn't know how to detect the
problem earlier on, so how could they have known"?
Dr. Kelleher adds that since it is known to have a genetic basis,
he believes that outside sources are unlikely to play a major role.
"My understanding is that the disease is autosomal recessive
with incomplete penetrance. This means that one gene from each
parent is required for a dog to develop symptoms (phenotype)
consistent with having two copies of the gene (genotype)."
He goes on with a brief overview of Mendelian Genetics. "The
probability of each puppy inheriting two copies of the gene from
affected parents is 100%. The probability of each puppy in a
litter born to parents that are carriers (heterozygous) is 25%
chance to have both affected copies (homozygous), 25% chance
to be clear, and 50% chance to be carriers (heterozygous). Dogs
without both affected copies will therefore be negative for
symptoms."
Dr. Kelleher explains that the test is not uniform across breeds,
even for those that do share similar SOD1 mutations. "This is
because there are specific locations along the gene called alleles
that are variable among breeds. In other words, the test does not
apply well to all breeds." He does believe, however, that in his
experience it is most accurate in predicting the risk of DM in
Corgis and GSDs.
"I believe genetic testing is in most cases a complement to other
pre-breeding health testing," he says. ";For example, it would be
ill-advised to breed a dog with a high PennHip distraction index
that is also a DM carrier. The DM carrier piece is less important
but when combined with another disease process (hip dysplasia)
that has a multifaceted genetic basis, you can use it to optimize
decision making."
Robert Westra, Associate Medical and Veterinary Market
Development Director at Neogen, another expert in the study of
DM, reiterates that one mutated copy of the SOD1 gene from
each parent is the factor for concern. "Having only one copy
creates a carrier who will not get the disease (per current
thinking). Because the mutation has recessive inheritance, a dog
that only inherits one copy of the mutation is not typically at risk
to develop clinical signs."
Many breeders who are not familiar with the mechanism of
inheritance, are ONLY breeding non-carriers to other non-
carriers which is of great concern, given the limiting of the
German Shepherd gene pool.
"Through genetic testing, we encourage the identification of
‘carriers’ not to eliminate them from the breeding population,
but rather to maintain them in any program by pairing them to
an appropriate ‘clear’ mate so the positive features and traits
within the ‘carrier’ have the potential to be conserved," he
answered. "At the same time, this breeding strategy will not
produce any ‘at-risk’ pups."
Dr. Westra counters, "It is possible that by selectively breeding
for certain other attributes, that some breeders may be including
affected dogs (homozygous) or carriers (heterozygous) in their
programs unintentionally." He mentions this is especially
plausible if testing is not performed prior to breeding."
There are other mutations we deal with that are more pertinent
to this question than DM," he adds. "These mutations are found
in such high frequency in a specific breed that if an aggressive
breeding strategy is adopted to eliminate the mutation, too many
dogs would be disqualified from breeding. That may lead to a
genetic bottleneck and may have deleterious consequences to the
breed."
In closing, Dr. Westra concluded that although the SOD 1 gene
mutation is responsible for the vast number of symptomatic
cases, there may be other genes that could play a role. "Other
breeds where this variant occurs but is not associated with DM
risk likely have genetic factors protecting them from this
disease. Because there is still so much to understand about
genetics we cannot say that a similar neurologic condition
arising from an unknown mutation does not exist."
So it is important to remember that even in breeds like the
German Shepherd, where DM association is recognized, many
dogs testing at-risk from the variant will live long lives and
never develop symptomatic disease.
Special Thank You To The Following:
Interviews:
Dr Joan R. Coates
Dr. Dan Kelleher
Dr. Robert Westra
https://embarkvet.com/breeders/resources/canine-genetics-
for-dog-breeders/health-spotlight/dm/
https://www.scientificamerican.com/article/mind-control-by-
cell/
https://www.caninejournal.com/degenerative-myelopathy/
http://vhc.missouri.edu/small-animal-hospital/neurology-
neurosurgery/facts-on-neurologic-diseases/degenerative-
myelopathy/
https://scitemed.com/article/2792/scitemed-cmt-2019-00105
https://www.sciencedaily.com/releases/2009/01/09012117412
4.htm
https://pubmed.ncbi.nlm.nih.gov/26432396/