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

Abstract

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.

Characterization of Neuronal Ceroid-Lipofuscinosis in 3 Cats

“…1 and 2). Retinal atrophy and pigment accumulation in NCL are commonly observed in the human infantile and juvenile forms 11,17 and some canine 13,14,22,28 and ovine forms, 12 but prior to the current report, retinal lesions have been reported only in 1 feline case. 4 It appears that intraneuronal lipopigment accumulation inversely correlates with neuronal loss in NCL.…”

Accumulation of glial fibrillary acidic protein and histone H4 in brain storage bodies of Tibetan terriers with hereditary neuronal ceroid lipofuscinosis

“…In the majority of these diseases, the major stored proteins are F 0 subunit c of mitochondrial ATP synthase, a 7.6 kDa hydrophobic protein (Buzy et al 1996;Hall et al 1991;Kominami et al 1992;Tyynela et al 1997b) and/or the 16 kDa V 0 subunit c of vacuolar ATPase (Palmer et al 1997). In other forms of the disease, saposins A and D aredog breeds (Awano et al 2006a, b;Jolly and Palmer 1995;Jolly et al 1992Jolly et al , 1994Katz et al 2001). In cases where the underlying mutation occurs in a gene orthologous to one of the human NCL genes, the major stored proteins have been found to be the same as in the corresponding human disorders.…”

Partial Correction of the CNS Lysosomal Storage Defect in a Mouse Model of Juvenile Neuronal Ceroid Lipofuscinosis by Neonatal CNS Administration of an Adeno-Associated Virus Serotype rh.10 Vector Expressing the Human CLN3 Gene

“…LFB staining can detect lipid accumulation in lysosomes ( Jolly et al, 1992;Mitchison et al, 1999;Sinha et al, 2004;Anzai et al, 2006;Haltia, 2006). When applied to brain sections of untreated Cln3…”

“…PAS is a classic method for detecting glycogen build up in lysosomes and accumulation of PAS-positive storage material has been demonstrated in JNCL patients ( Jolly et al, 1992;Sinha et al, 2004;Haltia, 2006). When applied to the brains of untreated Cln3…”