OMIA 000181-9940 : Neuronal Ceroid Lipofuscinosis, generic in Ovis aries

In other species: domestic cat , cattle , dog , horse , goat , pig , peach-faced lovebird , mallard , domestic ferret , crab-eating macaque

Possibly relevant human trait(s) and/or gene(s) (MIM number): 256730

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal Recessive

Considered a defect: yes

Key variant known: no

Cross-species summary: The neuronal ceroid lipofuscinoses (NCLs) are a heterogenous group of inherited neurodegenerative diseases characterised by brain and retinal atrophy and the accumulation of autofluorescent lipopigment in neurons and many other cells within the body. Clinical features of NCL are abnormal behavior, dementia, loss of vision, motor disturbances and seizures, and premature death. The disease has been described in humans (at least seven different variants), mice, dogs (English Setter, Border collie, Golden retriever, Australian cattle dog, Saluki, Chihuahua, Tibetian terier, Dachshund, and Miniature Schnauzer), Siamese cats, cattle (Beefmaster, Devon), Nubian goats, and sheep (South Hampshire, Rambouillet, Swedish Landrace, Merino) [Imke Tammen 21 Jan 2002].

Species-specific name: Neuronal ceroid lipofuscinosis

Species-specific description: Neuronal ceroid lipofuscinoses have been described in several sheep breeds (South Hampshire, Rambouillet, Swedish Landrace and Merino sheep). CONCL in Swedish Landrace sheep with congenital onset is distinct to OCL (ovine ceroid lipofuscinose) in South Hampshire, Rambouillet and Merino sheep where first clinical signs occur at about four to eight month of age. Tyynela et al. (2000) identified that a missense mutation in the ovine cathepsin D gene causes CONCL [Imke Tammen: 21 Jan 2002].

This disorder differs from all other forms of ceroid lipofuscinosis reported in sheep, in that the buildup of lipofuscins is confined to nervous tissue. Reported in a flock of Rambouillet sheep in the USA by Edwards et al. (1994).

Clinical features: Affected newborn lambs are weak, trembling, and unable to rise and support their body. Those who are able to support their head and suckle will only survive a few weeks with bottle feeding. [Imke Tammen: 21 Jan 2002]

Pathology: At autopsy, the brain of affected lambs is about halve the normal size. Histological studies of the brain show granular storage material in the cytoplasm of neurons, neuronal loss, reactive astrocytosis and infiltration of macrophages. Smaller amounts of similar storage material can be found in many extraneural cell types. The storage material can be strongly stained by luxol fast blue, PAS and Sudan black B methods and shows autofluorescence in ultraviolet light. Electron microscopy reveals granular osmiophilic deposits (GRODs) in the neuronal storage bodies. Immunohistochemical studies show that the storage material consists mainly of sphingoloipid activator proteins (SAPs) A and D. (In sheep with OCL the predominant storage material is mitochondrial ATP synthase subunit c) [Imke Tammen: 21 Jan 2002]

Breed: Rambouillet.

References


Note: the references are listed in reverse chronological order (from the most recent year to the earliest year), and alphabetically by first author within a year.
2006 Siintola, E., Lehesjoki, AE., Mole, SE. :
Molecular genetics of the NCLs - status and perspectives. Biochim Biophys Acta 1762:857-64, 2006. Pubmed reference: 16828266. DOI: 10.1016/j.bbadis.2006.05.006.
2002 Palmer, DN., Oswald, MJ., Westlake, VJ., Kay, GW. :
The origin of fluorescence in the neuronal ceroid lipofuscinoses (Batten disease) and neuron cultures from affected sheep for studies of neurodegeneration. Arch Gerontol Geriatr 34:343-57, 2002. Pubmed reference: 14764335.
2001 Hughes, S.M., Moroni-Rawson, P., Jolly, R.D., Jordan, T.W. :
Submitochondrial distribution and delayed proteolysis of subunit c of the H+-transporting ATP-synthase in ovine ceroid-lipofuscinosis Electrophoresis 22:1785-1794, 2001. Pubmed reference: 11425233. DOI: 10.1002/1522-2683(200105)22:9<1785::AID-ELPS1785>3.0.CO;2-L.
Katz, M.L., Shibuya, H., Johnson, G.S. :
Animal models for the ceroid lipofuscinoses. Adv Genet 45:183-203, 2001. Pubmed reference: 11332773.
1999 Hughes, S.M., Kay, G.W., Jordan, T.W., Rickards, G.K., Palmer, D.N. :
Disease-specific pathology in neurons cultured from sheep affected with ceroid lipofuscinosis Molecular Genetics & Metabolism 66:381-386, 1999.
Kay, G.W., Hughes, S.M., Palmer, D.N. :
In vitro culture of neurons from sheep with Batten disease Molecular Genetics & Metabolism 67:83-88, 1999.
1997 Jolly, R.D. :
The ovine model of neuronal ceroid lipofuscinosis (ncl) - its contribution to understanding the pathogenesis of batten-disease Neuropediatrics 28:60-62, 1997. Pubmed reference: 9151325. DOI: 10.1055/s-2007-973670.
1996 Lane, SC., Jolly, RD., Schmechel, DE., Alroy, J., Boustany, RM. :
Apoptosis as the mechanism of neurodegeneration in Batten's disease. J Neurochem 67:677-83, 1996. Pubmed reference: 8764595.
1995 Elleder, M., Drahota, Z., Lisa, V., Mares, V., Mandys, V., Muller, J., Palmer, D.N. :
Tissue culture loading test with storage granules from animal models of neuronal ceroid-lipofuscinosis (Batten disease): Testing their lysosomal degradability by normal and batten cells American Journal of Medical Genetics 57:213-221, 1995. Pubmed reference: 7668332. DOI: 10.1002/ajmg.1320570220.
Jolly, R.D. :
Comparative biology of the neuronal ceroid-lipofuscinoses (NCL): an overview. Am J Med Genet 57:307-11, 1995. Pubmed reference: 7668352. DOI: 10.1002/ajmg.1320570240.
Moronirawson, P., Palmer, D.N., Jolly, R.D., Jordan, T.W. :
Variant proteins in ovine ceroid-lipofuscinosis American Journal of Medical Genetics 57:279-284, 1995. Pubmed reference: 7668345. DOI: 10.1002/ajmg.1320570233.
Westlake, V.J., Jolly, R.D., Jones, B.R., Mellor, D.J., Machon, R., Zanjani, E.D., Krivit, W. :
Hematopoietic cell transplantation in fetal lambs with ceroid- lipofuscinosis American Journal of Medical Genetics 57:365-368, 1995. Pubmed reference: 7668364. DOI: 10.1002/ajmg.1320570252.
1994 Edwards, J.F., Storts, R.W., Joyce, J.R., Shelton, J.M., Menzies, C.S. :
Juvenile-Onset Neuronal Ceroid-Lipofuscinosis in Rambouillet Sheep Veterinary Pathology 31:48-54, 1994. Pubmed reference: 8140725.
Woods, P.R., Storts, R.W., Shelton, M., Menzies, C. :
Neuronal ceroid lipofuscinosis in Rambouillet sheep: characterization of the clinical disease. J Vet Intern Med 8:370-5, 1994. Pubmed reference: 7837115.
1993 Jolly, R.D. :
Round-Table Discussion of Animal Models of Ceroid- Lipofuscinosis (Batten Disease) Journal of Inherited Metabolic Disease 16:278-279, 1993. Pubmed reference: 8411980.
Jolly, R.D., Dalefield, R.R., Palmer, D.N. :
Ceroid, Lipofuscin and the Ceroid-Lipofuscinoses (Batten Disease) Journal of Inherited Metabolic Disease 16:280-283, 1993. Pubmed reference: 8411981.
Koppang, N. :
The Significance of Animal Models for Human Ceroid-Lipofuscinosis Journal of Inherited Metabolic Disease 16:272-273, 1993. Pubmed reference: 8411978.
Medd, S.M., Walker, J.E., Jolly, R.D. :
Characterization of the Expressed Genes for Subunit-c of Mitochondrial ATP Synthase in Sheep with Ceroid Lipofuscinosis Biochemical Journal 293:65-73, 1993. Pubmed reference: 8328973.
Woods, P. R, Walker, M. A, Weir, V. A, Storts, R. W, Menzies, C, Shelton, M :
Computed tomography of Rambouillet sheep affected with neuronal ceroid lipofuscinosis Veterinary Radiology &amp; Ultrasound 34:259-262, 1993.
1992 Jolly, R.D., Gibson, A.J., Healy, P.J., Slack, P.M., Birtles, M.J. :
Bovine Ceroid-Lipofuscinosis - Pathology of Blindness New Zealand Veterinary Journal 40:107-111, 1992.
Jolly, R.D., Martinus, R.D., Palmer, D.N. :
Sheep and Other Animals with Ceroid-Lipofuscinoses - Their Relevance to Batten Disease American Journal of Medical Genetics 42:609-614, 1992. Pubmed reference: 1535180. DOI: 10.1002/ajmg.1320420436.
Katz, M.L., Gerhardt, K.O. :
Methylated Lysine in Storage Body Protein of Sheep with Hereditary Ceroid-Lipofuscinosis Biochimica et Biophysica Acta 1138:97-108, 1992. Pubmed reference: 1540666.
1990 Fearnley, I.M., Walker, J.E., Martinus, R.D., Jolly, R.D., Kirkland, K.B., Shaw, G.J., Palmer, D.N. :
The Sequence of the Major Protein Stored in Ovine Ceroid Lipofuscinosis Is Identical with That of the Dicyclohexylcarbodiimide-Reactive Proteolipid of Mitochondrial ATP Synthase Biochemical Journal 268:751-758, 1990. Pubmed reference: 2141977.
Jolly, R.D., Martinus, R.D., Shimada, A., Fearnley, I.M., Palmer, D.N. :
Ovine Ceroid-Lipofuscinosis Is a Proteolipid Proteinosis Canadian Journal of Veterinary Research-Revue Canadienne de Recherche Veterinaire 54:15-21, 1990. Pubmed reference: 2306665.
Samuelson, D.A., Armstrong, D., Jolly, R. :
X-Ray Microprobe Analysis of the Retina and RPE in Sheep with Ovine Ceroid-Lipofuscinosis Neurobiology of Aging 11:663-667, 1990. Pubmed reference: 2280809.
1989 Jolly, R.D., Shimada, A., Dopfmer, I., Slack, P.M., Birtles, M.J., Palmer, D.N. :
Ceroid-Lipofuscinosis (Battens Disease) - Pathogenesis and Sequential Neuropathological Changes in the Ovine Model Neuropathology and Applied Neurobiology 15:371-383, 1989. Pubmed reference: 2779737.
1980 Jolly, RD., Janmaat, A., West, DM., Morrison, I. :
Ovine ceroid-lipofuscinosis: a model of Batten's disease. Neuropathol Appl Neurobiol 6:195-209, 1980. Pubmed reference: 6772982.

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  • Created by Izmira Ismail on 23 Jun 2006
  • Changed by Frank Nicholas on 14 Sep 2011
  • Changed by Frank Nicholas on 09 Dec 2011