Wisconsin Alumni Research Foundation

University of Pennsylvania

Charcot-Marie-Tooth Association

John Svaren

Peter Muir

Susannah Sample

Steven S Scherer

Taleen Hanania

David C Chan

Guojun Zhao

Mark Albert Scheideler

Methods for diagnosing propensity to exhibit acquired peripheral neuropathy in dogs are described. The methods and kits test dogs for presence of a disease-associated genomic variant. Presence of the genomic variant indicates an increased likelihood of the dog developing an acquired peripheral neuropathy. This information can be used to guide preemptive clinical treatment of the animal for peripheral neuropathy and to choose dogs for selective breeding programs.

Genetic testing for inherited peripheral neuropathy

The present invention relates to Charcot-Marie-Tooth disease 2A (CMT2A) harboring the p.Arg364Trp or p.His361Tyr Mfn2 mutation, whose human counterpart results in severe, early-onset axonal neuropathy for p.Arg364Trp Mfn2 mutation in fertilized rat eggs. Cohorts of mutants and wild type littermates were characterized with multiple motor deficits that worsened over time. Separate cohorts of mutant and wild type at 7, 40, and 48 weeks showed reduced density of myelinated axons and active axonal degeneration in distal but not proximal nerves, as well as axonal degeneration in the fasciculus gracilis of the cervical spinal cord at 40 and 48 weeks not present in 7-week-old cohort Mfn2 mutants, or wild type at 7 or 40 weeks. The p.His361Tyr Mfn2 mutation using CRISPR/Cas9 showed abnormalities in gait dynamics at 8 weeks and lengthening of gait cycle at 16 weeks. The invention provides progressive axonal neuropathy for examining pathogenesis and treatment of CMT2A.

Rat models for CMT2A that develop a progressive neuropathy

Methods and kits for diagnosing propensity to exhibit acquired peripheral neuropathy in dogs are described. The methods and kits test dogs for presence of a single-nucleotide polymorphism (SNP) TIGRP2P18586_rs8746233. Presence of the SNP indicates an increased likelihood of the dog exhibiting an acquired peripheral neuropathy. This information can be used to guide preemptive clinical treatment of the animal for peripheral neuropathy and to choose dogs for selective breeding programs.

Method to predict likelihood of inherited peripheral neuropathy in mammals

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Madison, WI, United States of America

John Svaren