Neuronal ceroid lipofuscinosis in Merino sheep

OBJECTIVE: To characterise neuronal ceroid lipofuscinosis (NCL) in Merino sheep. DESIGN: A prospective clinical, pathological, biochemical and genetic study. PROCEDURE: NCL cases were studied from a medium-wool Merino flock, the stud of origin of its replacement rams, and an experimental flock established at the University of Sydney. RESULTS: Behavioural changes and visual impairment were first detected at 7 to 12 months of age and progressed, with associated motor disturbances and at later stages seizures, to premature death by 27 months of age. At necropsy there was severe cerebrocortical atrophy associated with neuronal loss, astrocytosis and the presence in neurons of eosinophilic intracytoplasmic storage bodies with the characteristics of a lipopigment. In the retina there was progressive loss of photoreceptor cells. Storage bodies isolated from fresh brain, liver and pancreas formed electron-dense aggregates and coarse multilamellar and fine fingerprint profiles ultrastructurally, and consisted mainly of the hydrophobic protein, subunit c of mitochondrial ATP synthase. A homozygosity mapping approach localised the gene causing the disease in Merino sheep to the chromosomal region (OAR7q13-15) associated with NCL in South Hampshire sheep. CONCLUSION: NCL in Merino sheep is a subunit c-storing disease, clinically and pathologically similar to NCL in South Hampshire sheep. We propose that the disease in both breeds represents mutation at the same gene locus in chromosomal region OAR7q13-15.