Id |
Subject |
Object |
Predicate |
Lexical cue |
T1 |
109-121 |
DRI_Background |
denotes |
The neuronal |
T2 |
144-273 |
DRI_Background |
denotes |
(NCLs, Batten disease) are inherited neurodegenerative lysosomal storage diseases caused by mutations in several different genes. |
T3 |
274-391 |
DRI_Challenge |
denotes |
Mutations in CLN5 cause a variant late-infantile human disease and some cases of juvenile and adult clinical disease. |
T4 |
392-470 |
DRI_Background |
denotes |
NCLs also occur in animals, and a flock of New Zealand Borderdale sheep with a |
T5 |
488-534 |
DRI_Background |
denotes |
mutation has been developed for model studies. |
T6 |
535-757 |
DRI_Background |
denotes |
Dissociated mixed neural cells from CLN5-deficient foetal sheep brains contained no obvious storage bodies at plating but these accumulated rapidly in culture, mainly in microglial cells and also in neurons and astrocytes. |
T7 |
758-904 |
DRI_Background |
denotes |
Accumulation was very obvious after a week, as monitored by fluorescent microscopy and immunostaining for subunit c of mitochondrial ATP synthase. |
T8 |
905-1154 |
DRI_Background |
denotes |
Photography at intervals revealed the dynamic nature of the cultures and a flow of storage bodies between cells, specifically the phagocytosis of storage-body containing cells by microglia and incorporation of the storage bodies into the host cells. |
T9 |
1155-1205 |
DRI_Background |
denotes |
No storage was observed in cultured control cells. |
T10 |
1206-1379 |
DRI_Background |
denotes |
Transduction of cell cultures with a lentiviral vector expressing a C-terminal Myc tagged CLN5 resulted in secretion of post-translationally glycosylated and processed CLN5. |
T11 |
1380-1519 |
DRI_Outcome |
denotes |
Transduction of CLN5-deficient cultures with this construct rapidly reversed storage body accumulation, to less than half in only six days. |
T12 |
1520-1703 |
DRI_Background |
denotes |
These results show that storage body accumulation is reversible with enzyme correction and support the use of these cultures for testing of therapeutics prior to whole animal studies. |