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.

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Keywords Animal model, Batten disease, Borderdale sheep, CLN5, Lysosomal storage disease, NCL, mRNA splicing
Persistent URL dx.doi.org/10.1016/j.nbd.2007.09.006, hdl.handle.net/1765/29901
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Citation
Frugier, T, Mitchell, N.L, Tammen, I, Houweling, P.J, Arthur, D.G, Kay, G.W, … Palmer, D.N. (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