Ovine Ceroid‐lipofuscinosis: A Model of Batten's Disease

Jolly, R. D.; Janmaat, A.; West, D.M.; Morrison, Ian M.

doi:10.1111/j.1365-2990.1980.tb00290.x

Cited by 97 publications

(30 citation statements)

References 17 publications

(10 reference statements)

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“…The adult subclinical form of ceroid-lipofuscinosis in Tibetan Terriers [Riis, 19921 is clearly different from the other canine forms. The diseases in sheep [Jolly et al, 1980[Jolly et al, , 1982 and Devon cattle [Harper et al, 19881 are very similar and both include brain atrophy and retinal degeneration. As brain atrophy is a distinct component of the ceroid-lipofuscinoses as compared to other lysosoma1 storage diseases, it is important that it be measured or assessed in the development of any model.…”

Section: Models Of Ceroid-lipofuscinosismentioning

confidence: 98%

Sheep and other animals with ceroid‐lipofuscinoses: Their relevance to Batten disease

1992

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Distinct pathological and histopathological changes distinguish the ceroid-lipofuscinoses from other storage diseases of humans and animals. These various disease entities likely reflect a variety of mutations of the same gene, or mutations of different genes associated with metabolism of the same or similar substrates. The disease in sheep most closely resembles the juvenile human disease. In it 50% of the lipopigment consists of subunit c of mitochondrial ATP synthase while the remaining constituents are considered normal for a lysosomal derived cytosome. The same subunit c has been shown to be also stored in affected English Setter, Border Collie, and Tibetan Terrier dogs, the Devon cow, and in the late infantile and juvenile human forms of disease but not in the infantile form. Thus it gives a chemical unity to at least some members of the group and allows a major conceptual change in regard to further directions of research.

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Section: Models Of Ceroid-lipofuscinosismentioning

confidence: 98%

Sheep and other animals with ceroid‐lipofuscinoses: Their relevance to Batten disease

1992

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“…It has been suggested that the infantile form be considered as a separate type of disease and the name "polyunsaturated fatty acid lipidosis" has been proposed for it [Svennerholm, 19761. Most of these hypotheses are based on the presumed nature of the material in storage bodies or of compounds found at "elevated levels" in tissues, but until the present work there has been little systematic study of the composition of storage bodies in the human diseases. However, such studies have been made in a form of ceroid-lipofuscinosis in sheep, which is similar to both the juvenile and late infantile human forms [Jolly et al, 1980[Jolly et al, , 1982 Purified storage bodies were isolated from tissues of affected sheep, using a combination of osmotic shock, sonication, and low speed centrifugation [Palmer et al, 1986a;19881. These were analysed in order to determine the nature of the stored component, and thus to provide an insight into the defect or defects underlying the disease.…”

Section: Introductionmentioning

confidence: 99%

Mitochondrial ATP synthase subunit c storage in the ceroid‐lipofuscinoses (Batten disease)

et al. 1992

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The ceroid-lipofuscinoses (Batten disease) are neurodegenerative inherited lysosomal storage diseases of children and animals. A common finding is the occurrence of fluorescent storage bodies (lipopigment) in cells. These have been isolated from tissues of affected sheep. Direct protein sequencing established that the major component is identical to the dicyclohexylcarbodiimide (DCCD) reactive proteolipid, subunit c, of mitochondrial ATP synthase and that this protein accounts for at least 50% of the storage body mass. No other mitochondrial components are stored. Direct sequencing of storage bodies isolated from tissues of children with juvenile and late infantile ceroid-lipofuscinosis established that they also contain large amounts of complete and normal subunit c. It is also stored in the disease in cattle and dogs but is not present in storage bodies from the human infantile form. Subunit c is normally found as part of the mitochondrial ATP synthase complex and accounts for 2-4% of the inner mitochondrial membrane protein. Mitochondria from affected sheep contain normal amounts of this protein. The P1 and P2 genes that code for it are normal as are mRNA levels. Oxidative phosphorylation is also normal. These findings suggest that ovine ceroid-lipofuscinosis is caused by a specific failure in the degradation of subunit c after its normal inclusion into mitochondria, and its consequent abnormal accumulation in lysosomes. This implies a unique pathway for subunit c degradation. It is probable that the human late infantile and juvenile diseases and the disease in cattle and dogs involve lesions in the same pathway.

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“…Of the various reports describing ceroid lipofuscinosis in animals [1], only the En glish setter [10] and sheep models [9] have been inbred and are available for detailed experimental study. As decreased visual acuity and progressive retinal degeneration are prominent features of the human disease [2], longitudinal studies of electroretino graphic (ERG) and morphological changes [3,11,12] in the English setter have demon strated the uniqueness and importance of this animal model.…”

Section: Introductionmentioning

confidence: 99%

Retinal Pigment Epithelial Dysfunction in Early Ovine Ceroid Lipofuscinosis: Electrophysiologic and Pathologic Correlates

et al. 1985

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Retinal degeneration is a major finding in the human and ovine ceroid lipofuscinosis. Sequential electroretinographic (ERG) studies in a young, asymptomatic, affected lamb are presented here, which demonstrate a progressive loss of the scotopic b-wave and unrecordable c-waves under halothane anesthesia. Even at this initial stage of disease, lesions were evident in the form of dystrophic retinal pigment epithelial (RPE) villi, and loss of photoreceptor cells and rod outer segments. Cone inner segments were enlarged and scanning electron microscopy emphasized these abnormalities. All cells in tapetal and nontapetal areas contained fluorescent inclusions with similar emission spectra (maximum = 539 nm). By transmission electron microscopy, storage bodies consisted of ‘fingerprint’ profiles and were most prominent in bipolar cells. The pathological features of the retina correlate well with the observed ERG changes, reaffirming the sheep as a useful model to delineate early events in ceroid lipofuscinosis.

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Ovine Ceroid‐lipofuscinosis: A Model of Batten's Disease

Cited by 97 publications

References 17 publications

Sheep and other animals with ceroid‐lipofuscinoses: Their relevance to Batten disease

Sheep and other animals with ceroid‐lipofuscinoses: Their relevance to Batten disease

Mitochondrial ATP synthase subunit c storage in the ceroid‐lipofuscinoses (Batten disease)

Retinal Pigment Epithelial Dysfunction in Early Ovine Ceroid Lipofuscinosis: Electrophysiologic and Pathologic Correlates

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