TY  - JOUR
A1  - Somogyi, Aleksandra
A1  - Petcherski, Anton
A1  - Beckert, Benedikt
A1  - Huebecker, Mylene
A1  - Priestman, David A.
A1  - Banning, Antje
A1  - Cotman, Susan L.
A1  - Platt, Frances M.
A1  - Ruonala, Mika O.
A1  - Tikkanen, Ritva
T1  - Altered expression of ganglioside metabolizing enzymes results in GM3 ganglioside accumulation in cerebellar cells of a mouse model of juvenile neuronal ceroid lipofuscinosis
T2  - International journal of molecular sciences
N2  - Juvenile neuronal ceroid lipofuscinosis (JNCL) is caused by mutations in the CLN3 gene. Most JNCL patients exhibit a 1.02 kb genomic deletion removing exons 7 and 8 of this gene, which results in a truncated CLN3 protein carrying an aberrant C-terminus. A genetically accurate mouse model (Cln3Δex7/8 mice) for this deletion has been generated. Using cerebellar precursor cell lines generated from wildtype and Cln3Δex7/8 mice, we have here analyzed the consequences of the CLN3 deletion on levels of cellular gangliosides, particularly GM3, GM2, GM1a and GD1a. The levels of GM1a and GD1a were found to be significantly reduced by both biochemical and cytochemical methods. However, quantitative high-performance liquid chromatography analysis revealed a highly significant increase in GM3, suggesting a metabolic blockade in the conversion of GM3 to more complex gangliosides. Quantitative real-time PCR analysis revealed a significant reduction in the transcripts of the interconverting enzymes, especially of β-1,4-N-acetyl-galactosaminyl transferase 1 (GM2 synthase), which is the enzyme converting GM3 to GM2. Thus, our data suggest that the complex a-series gangliosides are reduced in Cln3Δex7/8 mouse cerebellar precursor cells due to impaired transcription of the genes responsible for their synthesis.
KW  - Batten disease
KW  - neuronal ceroid lipofuscinosis
KW  - CLN3
KW  - lysosomal storage disorders
KW  - glycosphingolipids
KW  - gangliosides
Y1  - 2018
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/45792
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-457925
N1  - This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).
VL  - 19
IS  - 2, Art. 625
SP  - 1
EP  - 18
PB  - Molecular Diversity Preservation International
CY  - Basel
ER  -