Leonberger dogs spontaneous axonal neuropathy research

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Abstract from 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,

California 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.