UCL Discovery
UCL home » Library Services » Electronic resources » UCL Discovery

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

Faller, KM; Bras, J; Sharpe, SJ; Anderson, GW; Darwent, L; Kun-Rodrigues, C; Alroy, J; ... Guerreiro, RJ; + view all (2016) The Chihuahua dog: A new animal model for neuronal ceroid lipofuscinosis CLN7 disease? Journal of Neuroscience Research , 94 (4) pp. 339-347. 10.1002/jnr.23710. Green open access

[thumbnail of Louro Guerreiro__The Chihuahua dog_a new animal model for Neuronal Ceroid Lipofuscinosis CLN7 disease.pdf]
Preview
Text
Louro Guerreiro__The Chihuahua dog_a new animal model for Neuronal Ceroid Lipofuscinosis CLN7 disease.pdf

Download (2MB) | Preview

Abstract

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.

Type: Article
Title: The Chihuahua dog: A new animal model for neuronal ceroid lipofuscinosis CLN7 disease?
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1002/jnr.23710
Publisher version: http://dx.doi.org/10.1002/jnr.23710
Language: English
Additional information: Copyright © 2016 Wiley Periodicals, Inc. All rights reserved. This is the peer reviewed version of the following Faller, KM; Bras, J; Sharpe, SJ; Anderson, GW; Darwent, L; Kun-Rodrigues, C; Alroy, J; (2016) The Chihuahua dog: A new animal model for neuronal ceroid lipofuscinosis CLN7 disease? Journal of Neuroscience Research , 94 (4) pp. 339-347 which has been published in final form at 10.1002/jnr.23710. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving, http://olabout.wiley.com/WileyCDA/Section/id-820227.html#terms
Keywords: MFSD8, lysosomal storage disorder, neurodegeneration
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Institute of Prion Diseases
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Institute of Prion Diseases > MRC Prion Unit at UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Neurodegenerative Diseases
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Genetics and Genomic Medicine Dept
URI: https://discovery.ucl.ac.uk/id/eprint/1481112
Downloads since deposit
0Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item