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.
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.
Frugier
Tony
T
Lincoln University, Agriculture and Life Sciences Division, Cell Biology Group, PO Box 84, Lincoln 7647, Canterbury, New Zealand.
Mitchell
Nadia L
NL
Tammen
Imke
I
Houweling
Peter J
PJ
Arthur
Donald G
DG
Kay
Graham W
GW
van Diggelen
Otto P
OP
Jolly
Robert D
RD
Palmer
David N
DN
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
D008565:Membrane Proteins