Chapter 11 The Neuronal Ceroid-lipofuscinoses (Batten Disease)

Neuronal Ceroid-Lipofuscinosis in a Holstein Steer

“…Some researchers have suggested apoptosis as the cause of this targeted neuron loss, whereas others have focused on metabolically active, mitochondrial-rich neurons suggested to be damaged because of mitochondrial dysfunction and chronic neuronal excitotoxicity. 7,9 The multilaminar ultrastructural characteristics of sections of the neuronal storage bodies in this young steer are most consistent with some storage of SCMAS. This extremely hydrophobic mitochondrial protein often forms insoluble complexes with lipids, and its accumulation in many NCLs has led to the theory that there may be a defect in its transport or degradation.…”

“…Human NCLs traditionally have been classified by age of onset combined with ultrastructural phenotype: granular osmiophilic deposits characteristic of SAPs versus the lamellar appearance of SCMAS. 5,9 However, most human NCLs are now classified on the basis of predicted or defined defects in 7 genes as CLN1 through 8. The CLN1 encodes palmitoyl-protein thioesterase, and the storage material accumulating in affected infants are SAPs, but SCMAS is the main component of the storage material in CLN2-8.…”

“…5,7 The inheritance of many animal and human NCLs has been determined to be recessive, and vision loss has been documented in both human and animal NCLs. 5,9,16 A 15-18-month-old Holstein steer with a history of progressive blindness was presented for slaughter. Grossly, the eyes were unremarkable with the exception of dilated pupils.…”

“…This extremely hydrophobic mitochondrial protein often forms insoluble complexes with lipids, and its accumulation in many NCLs has led to the theory that there may be a defect in its transport or degradation. 9 A yeast model in which a homologous gene for CLN3 was disrupted suggested that defects in the control of endosomal/lysosomal pH may play a role in this accumulation of SCMAS. 11 This inference was reinforced by the production of an NCL-like phenotype (including retinal atrophy) in a mouse model by the disruption of a gene coding for a chloride channel because the proposed pathogenesis also involved elevated endosomal pH.…”

Neuronal ceroid lipofuscinosis in Merino sheep

“…The biochemical analyses clearly identified NCL in Merino sheep as a subunit c-storing disease and implicate a change in a gene coding for a component of the subunit c turnover pathway. 2,26 The outcomes of matings in Flock 3 (approximately equal numbers of affected and unaffected offspring from mating of affected with suspected-heterozygous animals and absence of affected offspring from mating of an affected ram with outsourced ewes) were consistent with autosomal recessive inheritance of this disease. In Flock 1 it is likely that there was at least one heterozygous ram (and possibly more) among the 12 replacements rams purchased from Flock 2 and that the high rate of retention of female offspring for breeding ensured that there were sufficient numbers of heterozygous females in the flock to produce the NCL cases detected from 1996 to 1998.…”