Morphometric brain changes in an ovine CLN6 neuronal ceroid lipofuscinosis model — The Association Specialists

Morphometric brain changes in an ovine CLN6 neuronal ceroid lipofuscinosis model (21968)

Marianne D Keller 1 , Amelia C Nanni 2 , Marina G Gimeno 1 3 , Imke Tammen 1
  1. Sydney School of Veterinary Science, University of Sydney, Sydney, NSW, Australia
  2. School of Life and Environmental Sciences, University of Sydney, Sydney, NSW, Australia
  3. Elizabeth Macarthur Agricultural Institute, Department of Primary Industries, Menangle, NSW, Australia

Neuronal ceroid lipofuscinoses (NCL) or Batten Disease, is a group of genetic fatal paediatric neurodegenerative lysosomal storage disorders. The autosomal recessive subtype CLN6, occurs in humans as a late-infantile onset disease. It also naturally occurs in Merino and South Hampshire sheep, making them an ideal model for human disease. This study aimed to identify morphometric changes that occur in brains of 15-month-old Merino sheep which were homozygous for the Merino CLN6 variant (c.184C>T; p.(R62C)), compared to healthy, Merino control brains. The formalin-fixed brains of seven affected and three control sheep were scanned in a 9.4T Bruker MR scanner with a T1-weighted gradient echo (TE/TR=17.5/2500ms; voxel size= 0.4x0.4x0.8mm3). To facilitate soft tissue segmentation and volume quantification ‘Amira-avizo’ was used. Volumetric and statistical analysis found that the cerebellum and arbor vitae of affected sheep had an 11% and 9% reduction of their volume respectively, which was not significant compared to controls. However, the corpus callosum, striatum and thalamus of affected sheep experienced a significant loss of volume; 77%, 54% and 73% respectively, compared to controls. These findings are consistent with previous in-vivo studies of the South Hampshire CLN6 model, which is caused by a different genetic variant. Our study showed that MRI analysis of formalin-fixed tissues is more cost effective and allows for high resolution imaging. The affected brain regions can be used as biomarkers in the evaluation of therapeutic interventions for NCL as well as in routine assessments of disease progression through in-vivo MRI scans.