Altered Expression of Ganglioside Metabolizing Enzymes Results in GM3 Ganglioside Accumulation in Cerebellar Cells of a Mouse Model of Juvenile Neuronal Ceroid Lipofuscinosis
| العنوان: | Altered Expression of Ganglioside Metabolizing Enzymes Results in GM3 Ganglioside Accumulation in Cerebellar Cells of a Mouse Model of Juvenile Neuronal Ceroid Lipofuscinosis |
|---|---|
| المؤلفون: | Anton Petcherski, Aleksandra Somogyi, Ritva Tikkanen, Frances M. Platt, David A. Priestman, Mylene Huebecker, Benedikt Beckert, Susan L. Cotman, Antje Banning, Mika O. Ruonala |
| المصدر: | International Journal of Molecular Sciences; Volume 19; Issue 2; Pages: 625 International Journal of Molecular Sciences, Vol 19, Iss 2, p 625 (2018) International Journal of Molecular Sciences |
| بيانات النشر: | Multidisciplinary Digital Publishing Institute, 2018. |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | 0301 basic medicine, Batten disease, lcsh:Chemistry, Exon, Mice, 0302 clinical medicine, Cerebellum, Gangliosides, lcsh:QH301-705.5, Spectroscopy, Membrane Glycoproteins, glycosphingolipids, Chemistry, CLN3, General Medicine, gangliosides, Computer Science Applications, Neuronal ceroid lipofuscinosis, lipids (amino acids, peptides, and proteins), neuronal ceroid lipofuscinosis, lysosomal storage disorders, Cholera Toxin, endocrine system, Lysosomal storage disorders, Catalysis, Article, Glycosphingolipids, Inorganic Chemistry, 03 medical and health sciences, Neuronal Ceroid-Lipofuscinoses, Precursor cell, medicine, Animals, G(M3) Ganglioside, ddc:610, Physical and Theoretical Chemistry, Molecular Biology, Gene, Ganglioside, Organic Chemistry, Wild type, medicine.disease, Molecular biology, carbohydrates (lipids), Disease Models, Animal, 030104 developmental biology, lcsh:Biology (General), lcsh:QD1-999, Lysosomes, 030217 neurology & neurosurgery, Molecular Chaperones |
| الوصف: | 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 (Cln3(ex7/8) mice) for this deletion has been generated. Using cerebellar precursor cell lines generated from wildtype and Cln3(ex7/8) 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 -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 Cln3(ex7/8) mouse cerebellar precursor cells due to impaired transcription of the genes responsible for their synthesis. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 1422-0067 |
| DOI: | 10.3390/ijms19020625 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::999b4a63ee62f082c76105c6bee573d6Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....999b4a63ee62f082c76105c6bee573d6 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14220067 |
|---|---|
| DOI: | 10.3390/ijms19020625 |