title: Rapid and Progressive Regional Brain Atrophy in CLN6 Batten Disease Affected Sheep Measured with Longitudinal Magnetic Resonance Imaging.
abstract: Variant late-infantile Batten disease is a neuronal ceroid lipofuscinosis caused by mutations in CLN6. It is a recessive genetic lysosomal storage disease characterised by progressive neurodegeneration. It starts insidiously and leads to blindness, epilepsy and dementia in affected children. Sheep that are homozygous for a natural mutation in CLN6 have an ovine form of Batten disease Here, we used in vivo magnetic resonance imaging to track brain changes in 4 unaffected carriers and 6 affected Batten disease sheep. We scanned each sheep 4 times, between 17 and 22 months of age. Cortical atrophy in all sheep was pronounced at the baseline scan in all affected Batten disease sheep. Significant atrophy was also present in other brain regions (caudate, putamen and amygdala). Atrophy continued measurably in all of these regions during the study. Longitudinal MRI in sheep was sensitive enough to measure significant volume changes over the relatively short study period, even in the cortex, where nearly 40% of volume was already lost at the start of the study. Thus longitudinal MRI could be used to study the dynamics of progression of neurodegenerative changes in sheep models of Batten disease, as well as to assess therapeutic efficacy.
authors.affiliation: Department of Physiology, Development and Neuroscience, University of Cambridge, Downing Street, Cambridge, UK; Wolfson Brain Imaging Centre, University of Cambridge, Box 65 Addenbrooke's Hospital, Hills Road, Cambridge, United Kingdom.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Sawiak
authors.affiliation: South Australian Research and Development Institute, Roseworthy, South Australia.
authors.forename: Sunthara Rajan
authors.initials: SR
authors.lastname: Perumal
authors.affiliation: Preclinical, Imaging and Research Laboratories, South Australian Health and Medical Research Institute, Gilles Plains, South Australia.
authors.forename: Skye R
authors.initials: SR
authors.lastname: Rudiger
authors.affiliation: South Australian Research and Development Institute, Roseworthy, South Australia.
authors.forename: Loren
authors.initials: L
authors.lastname: Matthews
authors.affiliation: Department of Molecular Biosciences, Faculty of Agriculture and Life Sciences and Batten Animal Research Network, Lincoln University, Lincoln, New Zealand.
authors.forename: Nadia L
authors.initials: NL
authors.lastname: Mitchell
authors.affiliation: Preclinical, Imaging and Research Laboratories, South Australian Health and Medical Research Institute, Gilles Plains, South Australia.
authors.forename: Clive J
authors.initials: CJ
authors.lastname: McLaughlan
authors.affiliation: Preclinical, Imaging and Research Laboratories, South Australian Health and Medical Research Institute, Gilles Plains, South Australia.
authors.forename: C Simon
authors.initials: CS
authors.lastname: Bawden
authors.affiliation: Department of Molecular Biosciences, Faculty of Agriculture and Life Sciences and Batten Animal Research Network, Lincoln University, Lincoln, New Zealand.
authors.forename: David N
authors.initials: DN
authors.lastname: Palmer
authors.affiliation: South Australian Research and Development Institute, Roseworthy, South Australia.
authors.forename: Timothy
authors.initials: T
authors.lastname: Kuchel
authors.affiliation: Department of Physiology, Development and Neuroscience, University of Cambridge, Downing Street, Cambridge, UK.
authors.forename: A Jennifer
authors.initials: AJ
authors.lastname: Morton
mesh_terms: D000818:Animals; D001284:Atrophy; D001835:Body Weight; D001921:Brain / Q000473:pathology*; D018450:Disease Progression; D005260:Female; D008279:Magnetic Resonance Imaging; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D009472:Neuronal Ceroid-Lipofuscinoses / Q000473:pathology*; D009929:Organ Size; D010641:Phenotype; D012756:Sheep
chemical_list: D008565:Membrane Proteins