Increased α‐tocopherol metabolism in horses with equine neuroaxonal dystrophy

Autor: Erin N. Hales, Hadi Habib, Gianna Favro, Scott Katzman, R. Russell Sakai, Sabin Marquardt, Matthew H. Bordbari, Brittni Ming‐Whitfield, Janel Peterson, Anna R. Dahlgren, Victor Rivas, Carolina Alanis Ramirez, Sichong Peng, Callum G. Donnelly, Bobbi‐Sue Dizmang, Angelica Kallenberg, Robert Grahn, Andrew D. Miller, Kevin Woolard, Benjamin Moeller, Birgit Puschner, Carrie J. Finno
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Zdroj: Journal of Veterinary Internal Medicine, Vol 35, Iss 5, Pp 2473-2485 (2021)
Druh dokumentu: article
ISSN: 1939-1676
0891-6640
DOI: 10.1111/jvim.16233
Popis: Abstract Background Equine neuroaxonal dystrophy/equine degenerative myeloencephalopathy (eNAD/EDM) is an inherited neurodegenerative disorder associated with a vitamin E deficiency within the first year of life. Vitamin E consists of 8 isoforms metabolized by the CYP4F2 enzyme. No antemortem diagnostic test currently exists for eNAD/EDM. Hypothesis/Objectives Based on the association of α‐tocopherol deficiency with the development of eNAD/EDM, we hypothesized that the rate of α‐tocopherol, but not γ‐tocopherol or tocotrienol metabolism, would be increased in eNAD/EDM‐affected horses. Animals Vitamin E metabolism: Proof of concept (POC) study; eNAD/EDM‐affected (n = 5) and control (n = 6) horses. Validation study: eNAD/EDM‐affected Quarter Horses (QHs; n = 6), cervical vertebral compressive myelopathy affected (n = 6) horses and control (n = 29) horses. CYP4F2 expression and copy number: eNAD/EDM‐affected (n = 12) and age‐ and sex‐matched control (n = 11‐12) horses. Methods The rates of α‐tocopherol/tocotrienol and γ‐tocopherol/tocotrienol metabolism were assessed in equine serum (POC and validation) and urine (POC only) using liquid chromatography tandem mass spectrometry (LC‐MS/MS). Quantitative reverse‐transcriptase PCR (qRT‐PCR) and droplet digital (dd)‐PCR were used to assay expression and genomic copy number of a CYP4F2 equine ortholog. Results Metabolic rate of α‐tocopherol was increased in eNAD/EDM horses (POC,P
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