The Chihuahua dog: A new animal model for neuronal ceroid lipofuscinosis CLN7 disease?

Faller, K. M.E. et al. (2016) The Chihuahua dog: A new animal model for neuronal ceroid lipofuscinosis CLN7 disease? Journal of Neuroscience Research, 94(4), pp. 339-347. (doi:10.1002/jnr.23710) (PMID:26762174)

117146.pdf - Accepted Version



Neuronal ceroid lipofuscinoses (NCLs) are a group of incurable lysosomal storage disorders characterized by neurodegeneration and accumulation of lipopigments mainly within the neurons. We studied two littermate Chihuahua dogs presenting with progressive signs of blindness, ataxia, pacing, and cognitive impairment from 1 year of age. Because of worsening of clinical signs, both dogs were euthanized at about 2 years of age. Postmortem examination revealed marked accumulation of autofluorescent intracellular inclusions within the brain, characteristic of NCL. Whole-genome sequencing was performed on one of the affected dogs. After sequence alignment and variant calling against the canine reference genome, variants were identified in the coding region or splicing regions of four previously known NCL genes (CLN6, ARSG, CLN2 [=TPP1], and CLN7 [=MFSD8]). Subsequent segregation analysis within the family (two affected dogs, both parents, and three relatives) identified MFSD8:p.Phe282Leufs13*, which had previously been identified in one Chinese crested dog with no available ancestries, as the causal mutation. Because of the similarities of the clinical signs and histopathological changes with the human form of the disease, we propose that the Chihuahua dog could be a good animal model of CLN7 disease.

Item Type:Articles
Glasgow Author(s) Enlighten ID:Faller, Ms Kiterie and Penderis, Professor Jacques and Gutierrez Quintana, Mr Rodrigo
Authors: Faller, K. M.E., Bras, J., Sharpe, S. J., Anderson, G. W., Darwent, L., Kun-Rodrigues, C., Alroy, J., Penderis, J., Mole, S. E., Gutierrez Quintana, R., and Guerreiro, R. J.
College/School:College of Medical Veterinary and Life Sciences > School of Veterinary Medicine
Journal Name:Journal of Neuroscience Research
ISSN (Online):1097-4547
Published Online:13 January 2016
Copyright Holders:Copyright © 2016 Wiley
First Published:First published in Journal of Neuroscience Research 94(4):339-347
Publisher Policy:Reproduced in accordance with the copyright policy of the publisher

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