The project seeks to define the inborn biochemical anomaly in the ceroid- lipofuscinoses (Batten's disease) using the ovine model and to extend this knowledge to the analogous diseases of children. It particularly explores the observations that most forms of ceroid-lipofuscinosis specifically store the proteolipid, subunit c of mitochondrial ATP synthase. As the primary defect may not be lysosomal, research will focus on lysosomal, cytosolic and mitochondrial cell compartments seeking for abnormalities in the metabolism or transport of subunit c. Methodologies will include light and electron microscopy, immunocytochemistry, 2 directional electrophoresis, LDS PAGE, HPLC, tissue culture, differential centrifugation and enzymology, molecular genetics and direct in vivo studies. Definition of the underlying defect would have significance for better methods of diagnosis, including prenatal diagnosis and heterozygote detection as a basis to control of the disease. It may have relevance to therapy. Given the significance of the mitochondrial ATP synthase complex, the project will also have relevance to further understanding of its assembly and disassembly.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Research Project (R01)
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Special Emphasis Panel (SRC (55))
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Massey University
Palmerston North
New Zealand
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Jolly, R D; Brown, S; Das, A M et al. (2002) Mitochondrial dysfunction in the neuronal ceroid-lipofuscinoses (Batten disease). Neurochem Int 40:565-71
Hughes, S M; Moroni-Rawson, P; Jolly, R D et al. (2001) Submitochondrial distribution and delayed proteolysis of subunit c of the H+-transporting ATP-synthase in ovine ceroid-lipofuscinosis. Electrophoresis 22:1785-94
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Palmer, D N; Jolly, R D; van Mil, H C et al. (1997) Different patterns of hydrophobic protein storage in different forms of neuronal ceroid lipofuscinosis (NCL, Batten disease). Neuropediatrics 28:45-8
Jolly, R D; Walkley, S U (1997) Lysosomal storage diseases of animals: an essay in comparative pathology. Vet Pathol 34:527-48
Palmer, D N; Bayliss, S L; Westlake, V J (1995) Batten disease and the ATP synthase subunit c turnover pathway: raising antibodies to subunit c. Am J Med Genet 57:260-5
Jolly, R D; Palmer, D N (1995) The neuronal ceroid-lipofuscinoses (Batten disease): comparative aspects. Neuropathol Appl Neurobiol 21:50-60
Moroni-Rawson, P; Palmer, D N; Jolly, R D et al. (1995) Variant proteins in ovine ceroid-lipofuscinosis. Am J Med Genet 57:279-84

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