Clinical Application of Current Research Findings Toward the Prevention and Treatment of Acute Laminitis in Horses With Systemic Inflammatory Diseases: An Internist’s Perspective

Laminitis is most commonly caused by metabolic disorders or systemic inflammatory diseases. There are numerous recent publications that have reported on pathophysiology of laminitis associated with systemic inflammation. These studies include both in-vitro and in-vivo models investigating inflammatory profiles, vascular reactivity or oxidative stress at different stages of development or clinical laminitis and some studies have proposed therapeutic interventions. Although the amount of information in these studies is great and quality of the research is often outstanding, it has not always been clear how these findings might be applied to clinical practice. This article is intended to report one internist's perspective on recent research findings on the pathophysiology and prevention of laminitis in horses with systemic inflammatory diseases and how these findings might be applied to clinical practice.     

Pedigree Analysis and Exclusion of Alpha‐Tocopherol Transfer Protein (TTPA) as a Candidate Gene for Neuroaxonal Dystrophy in the American Quarter Horse

Background

Equine neuroaxonal dystrophy/equine degenerative myeloencephalopathy (NAD/EDM) is a neurodegenerative disorder affecting young horses of various breeds that resembles ataxia with vitamin E deficiency in humans, an inherited disorder caused by mutations in the alpha‐tocopherol transfer protein gene (TTPA). To evaluate variants found upon sequencing TTPA in the horse, the mode of inheritance for NAD/EDM had to be established.

Hypothesis

NAD/EDM in the American Quarter Horse (QH) is caused by a mutation in TTPA.

Animals

88 clinically phenotyped (35 affected [ataxia score ≥2], 53 unaffected) QHs with a diagnosis of NAD/EDM with 6 affected and 4 unaffected cases confirmed at postmortem examination.

Procedures

Pedigrees and genotypes across 54,000 single nucleotide polymorphism (SNP) markers were assessed to determine heritability and mode of inheritance of NAD/EDM. TTPA sequence of exon/intron boundaries was evaluated in 2 affected and 2 control horses. An association analysis was performed by 71 SNPs surrounding TTPA and 8 SNPs within TTPA that were discovered by sequencing. RT‐PCR for TTPA was performed on mRNA from the liver of 4 affected and 4 control horses.

Results

Equine NAD/EDM appears to be inherited as a polygenic trait and, within this family of QHs, demonstrates high heritability. Sequencing of TTPA identified 12 variants. No significant association was found using the 79 available variants in and surrounding TTPA. RT‐PCR yielded PCR products of equivalent sizes between affected cases and controls.

Conclusions and Clinical Importance

NAD/EDM demonstrates heritability in this family of QHs. Variants in TTPA are not responsible for NAD/EDM in this study population.