title: 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.
abstract: 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.
authors.affiliation: Lincoln University, Agriculture and Life Sciences Division, Cell Biology Group, PO Box 84, Lincoln 7647, Canterbury, New Zealand.
authors.forename: Tony
authors.initials: T
authors.lastname: Frugier
authors.forename: Nadia L
authors.initials: NL
authors.lastname: Mitchell
authors.forename: Imke
authors.initials: I
authors.lastname: Tammen
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Houweling
authors.forename: Donald G
authors.initials: DG
authors.lastname: Arthur
authors.forename: Graham W
authors.initials: GW
authors.lastname: Kay
authors.forename: Otto P
authors.initials: OP
authors.lastname: van Diggelen
authors.forename: Robert D
authors.initials: RD
authors.lastname: Jolly
authors.forename: David N
authors.initials: DN
authors.lastname: Palmer
mesh_terms: D000818:Animals; D004252:DNA Mutational Analysis / Q000379:methods; D004195:Disease Models, Animal; D005091:Exons / Q000235:genetics*; D008040:Genetic Linkage; D007515:Islets of Langerhans / Q000473:pathology / Q000648:ultrastructure; D007962:Leukocytes / Q000473:pathology; D008565:Membrane Proteins / Q000235:genetics*; D046529:Microscopy, Electron, Transmission; D008969:Molecular Sequence Data; D009472:Neuronal Ceroid-Lipofuscinoses / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D017354:Point Mutation; D012757:Sheep Diseases; D034561:Sheep, Domestic
chemical_list: D008565:Membrane Proteins