Re: Man's best friend recruited in the hunt for disease genes

[Guest guest]

Gretchen - what a great article! It is so informative and gives hope!

[Guest guest]

Hi ,

Back in 2003 there was an interesting piece of research on the

Leonberger dogs and inherited peripheral neuropathy, mentioning CMT. Below is a

repost of the abstract. After I read about the entire research projectI wrote an

article about it for CMT World magazine, but it's not on-line anywhere. If you'd

like a copy, I can dig through my files and snail mail you a paper copy.

If you go back into last months archives, there is an abstract about

Demyelinating polyneuropathy with focally folded myelin sheaths in a family of

Miniature Schnauzer dogs. There is a well established base of neuropathy

research on other dogs too.

Gretchen

Muscle Nerve. 2003 Apr;27(4):471-7.

Inherited polyneuropathy in Leonberger dogs: a mixed or intermediate

form of Charcot-Marie-Tooth disease?

Shelton GD, Podell M, Poncelet L, Schatzberg S, E,

HC, Mizisin AP.

Department of Pathology, University of California, San Diego, La

Jolla 92093-0612, USA.

A spontaneous distal, symmetrical polyneuropathy in related

Leonberger dogs with onset between 1 to 9 years of age was

characterized clinically, electrophysiologically, histologically, and

morphometrically.

Exercise intolerance and weakness was associated with a high-steppage

pelvic-limb gait, a loss or change in the pitch of the bark, and dyspnea.

Neurological examination revealed marked atrophy of the distal limb muscles,

depressed spinal and cranial nerve reflexes, and weak or absent movement of the

laryngeal and pharyngeal muscles.

Electrophysiological evaluation was consistent with denervation and was

characterized by loss or marked attenuation of compound muscle action potentials

and slowed motor nerve conduction velocity. Muscle biopsy specimens showed

neurogenic atrophy.

Chronic nerve fiber loss associated with decreased myelinated fiber density and

a shift of the axonal size-frequency distribution toward smaller fibers was the

predominant finding in peripheral nerve specimens.

Pedigree analysis of a large multigenerational family, including nine sibships

with at least one affected individual, suggested X-linked inheritance.

Mutational and linkage analysis of this family may aid in identification of the

chromosomal loci and gene responsible for this inherited axonal neuropathy.

Further characterization of this inherited axonal neuropathy may establish the

Leonberger dog as a spontaneous animal model of inherited axonal neuropathy and

possibly lead to the discovery of a new gene or genes associated with axonal

variants.

[Guest guest]

Hello everyone,

Could someone please tell me, is this true ? Someone is really doing research on

Dogs that have neuropathy or am I misunderstanding ?

Laine

[Guest guest]

I'm not directing this to anyone, but I think that " MAN " has lost his compassion

for animals. I find this research totally disgusting. I would rather have my CMT

than find a cure through animal testing, no matter how bad I get.

Lainie

[Guest guest]

Laine,

Let me clarify something. The dogs in research that I mentioned had

developed neuropathy first, it was in their DNA. They were not

specifically bred for research as mice are. These dogs were already

suffering from neuropathies and the vet's research stemmed from that.

Gretchen

[Guest guest]

Laine,

From what I've read the dogs start having ataxia (balance problems)

and their gait is altered. The vets do some testing, biopsy, and

believe it or not EMG type tests. This is how they found out about

the demyelination problem. They also study pedigree lineage for

genetic patterns, and some post-mortem observation.

I think this abstract on Min. Schnauzers is pretty clear as an

example. (I think I posted this before, but can't remember, lol)

Gretchen

J Neurol Sci. 2008 Sep 20.

Demyelinating polyneuropathy with focally folded myelin sheaths in a

family of Miniature Schnauzer dogs.

Vanhaesebrouck AE, Couturier J, Cauzinille L, Mizisin AP, Shelton GD,

Granger N.

National Veterinary School of Alfort, Maisons-Alfort, France.

A spontaneous demyelinating polyneuropathy in two young Miniature

Schnauzer dogs was characterized clinically, electrophysiologically

and histopathologically. Both dogs were related and a third dog,

belonging to the same family, had similar clinical signs.

On presentation, clinical signs were restricted to respiratory

dysfunction. Electrophysiological tests showed a dramatic decrease in

both motor and sensory nerve conduction velocities. Microscopic

examination of peripheral nerve biopsies (light and electron

microscopy, teased nerve fibers), showed that this

neuropathy was characterized by segmental demyelination and focally

folded myelin sheaths.

Various clinical syndromes associated with tomacula or focal

thickening of the myelin sheath of the peripheral nerves have been

described in humans and shown to be caused by gene mutations

affecting the myelin proteins, such as the hereditary neuropathy with

liability to pressure palsies or the demyelinating forms of Charcot-

Marie-Tooth disease.

In animals, a tomaculous neuropathy has been reported in cattle and

chickens but not in carnivores. Here we report a demyelinating

peripheral neuropathy with tomacula in two Miniature Schnauzer dogs.

[Guest guest]

Gretchen

Thank you for the information, I just don't believe in any type of animal

testing, but I'm sure I could find a few humans that they should use.

I thank you again for all your hard work, you do a wonderful job.

Laine