Batten disease (neuronal ceroid lipofuscinoses, NCLs) are a group of inherited childhood diseases that result in severe brain atrophy, blindness and seizures, leading to premature death. To date, eight different genes have been identified, each associated with a different form. Linkage analysis indicated a CLN5 form in a colony of affected New Zealand Borderdale sheep. Sequencing studies established the disease-causing mutation to be a substitution at a consensus splice site (c.571 + 1G > A), leading to the excision of exon 3 and a truncated putative protein. A molecular diagnostic test has been developed based on the excision of exon 3. Sequence alignments support the gene product being a soluble lysosomal protein. Western blotting of isolated storage bodies indicates the specific storage of subunit c of mitochondrial ATP synthase. This flock is being expanded as a large animal model for mechanistic studies and trial therapies.

, , , , , ,
doi.org/10.1016/j.nbd.2007.09.006, hdl.handle.net/1765/29901
Neurobiology of Disease
Erasmus MC: University Medical Center Rotterdam

Frugier, T., Mitchell, N., Tammen, I., Houweling, P., Arthur, D., Kay, G., … Palmer, D. (2008). A new large animal model of CLN5 neuronal ceroid lipofuscinosis in Borderdale sheep is caused by a nucleotide substitution at a consensus splice site (c.571 + 1G >>> A) leading to excision of exon 3. Neurobiology of Disease, 29(2), 306–315. doi:10.1016/j.nbd.2007.09.006