title: High resolution MRI reveals global changes in brains of Cln3 mutant mice.
abstract: Batten disease, the juvenile-onset form of neuronal ceroid lipofuscinosis (NCL), is a progressive neurodegenerative disorder of childhood with an age of onset of 5-10 years of age. JNCL is caused by mutations in the CLN3 gene which encodes a membrane protein of unknown function. Magnetic resonance imaging of the brain of juvenile NCL patients has revealed changes in signal intensity and tissue atrophy, predominantly in the cortex and cerebellum. A mouse model for Batten disease was created by targeted disruption of the murine Cln3 gene in order to further understanding of the pathophysiology of Batten disease and to evaluate potential therapeutic approaches. Several features of the disease are displayed by Cln3 mice including accumulation of characteristic storage material in neurons. The aim of this work was to investigate neurodegeneration in the Cln3 mouse model using high resolution magnetic resonance imaging to measure signal intensity ratios in selected regions of interest. Global changes were observed in the brains of 12-month-old mutant mice that mirror those seen in juvenile NCL patients. There is a decrease in signal intensity ratio in grey matter regions including cortex, hippocampus and cerebellum, tissues where neuronal storage accumulation and cell loss have been seen in the mouse model. The alterations seen in Cln3 mutant mice support the validity of further imaging studies and suggest that this method will have application in assessment of therapeutic approaches in the study of mutant mouse models of NCL including the Cln3 mouse.
authors.affiliation: Department of Paediatrics, Royal Free and University College Medical School, London, UK.
authors.forename: N D
authors.initials: ND
authors.lastname: Greene
authors.forename: M F
authors.initials: MF
authors.lastname: Lythgoe
authors.forename: D L
authors.initials: DL
authors.lastname: Thomas
authors.forename: R L
authors.initials: RL
authors.lastname: Nussbaum
authors.forename: D J
authors.initials: DJ
authors.lastname: Bernard
authors.forename: H M
authors.initials: HM
authors.lastname: Mitchison
mesh_terms: D000818:Animals; D001284:Atrophy; D001921:Brain / Q000473:pathology*; D004195:Disease Models, Animal; D008279:Magnetic Resonance Imaging; D008297:Male; D008562:Membrane Glycoproteins; D051379:Mice; D008817:Mice, Mutant Strains; D018832:Molecular Chaperones; D009472:Neuronal Ceroid-Lipofuscinoses / Q000235:genetics / Q000473:pathology*; D011506:Proteins / Q000235:genetics*
chemical_list: C105199:CLN3 protein, human; D008562:Membrane Glycoproteins; D018832:Molecular Chaperones; D011506:Proteins