Altered Expression of Ganglioside Metabolizing Enzymes Results in GM3 Ganglioside Accumulation in Cerebellar Cells of a Mouse Model of Juvenile Neuronal Ceroid Lipofuscinosis

International Journal of Molecular Sciences
Aleksandra SomogyiRitva Tikkanen

Abstract

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 imp...Continue Reading

References

Jan 10, 1975·Science·P H FishmanM Cornblath
Oct 1, 1991·Journal of the Neurological Sciences·M Trbojevic-CepeI Pavlicek
Jan 19, 1973·Biochimica Et Biophysica Acta·G TettamantiV Zambotti
Oct 1, 1996·Proceedings of the National Academy of Sciences of the United States of America·K TakamiyaS Aizawa
Jul 21, 1998·Annals of the New York Academy of Sciences·C L Schengrund, C M Mummert
Jul 21, 1998·Annals of the New York Academy of Sciences·M Alter
Mar 5, 1999·Biochimica Et Biophysica Acta·H J MaccioniJ A Martina
Apr 7, 1999·Molecular Genetics and Metabolism·R E HaskellB L Davidson
Apr 7, 1999·Molecular Genetics and Metabolism·K L PuranamR M Boustany
Jun 23, 1999·Proceedings of the National Academy of Sciences of the United States of America·K A SheikhR L Schnaar
Jan 3, 2001·The Journal of Biological Chemistry·H KawaiR L Proia
Apr 17, 2004·Journal of Lipid Research·Robert K YuGuichao Zeng
Jul 2, 2004·Glycoconjugate Journal·G Tettamanti
Jul 9, 2004·Pediatric Research·Dixie-Ann Persaud-SawinRose-Mary N Boustany
Oct 28, 2005·Human Molecular Genetics·Denia Ramirez-Montealegre, David A Pearce
May 23, 2006·The Journal of Biological Chemistry·Yi CaoSusan L Cotman
Jul 21, 2006·Biochimica Et Biophysica Acta·Thomas Kolter, Konrad Sandhoff
Oct 3, 2006·Nature Biotechnology·Walter SchubertAndreas W M Dress
Oct 31, 2006·Neurobiology of Disease·Ming J LimDavid A Pearce
Sep 22, 2007·Journal of Neurochemistry·Sathaporn NgamukoteRobert K Yu
Dec 6, 2007·Journal of Neurochemistry·Hugo J F Maccioni
Feb 9, 2008·Neurobiology of Aging·Alexandra BernardoMichael P McDonald
Mar 5, 2008·Pediatric Research·Elena RusynRose-Mary N Boustany
Oct 11, 2008·Journal of Lipid Research·Robert K YuMakoto Yanagisawa
Jan 2, 2009·Journal of Cell Science·Naoki IchikawaEri Arikawa-Hirasawa
Jun 27, 2009·Science·Marco SardielloAndrea Ballabio
Aug 25, 2009·Current Opinion in Structural Biology·Roland Schauer
Oct 14, 2009·FEBS Letters·Ronald L Schnaar
Mar 9, 2010·Journal of the Neurological Sciences·Jay S SchneiderFranca Cambi
Mar 20, 2010·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Vittorio MaglioneSimonetta Sipione
Jun 24, 2011·IUBMB Life·Jose Luis Daniotti, Ramiro Iglesias-Bartolomé
Jul 15, 2011·Human Molecular Genetics·Michela PalmieriAndrea Ballabio
Feb 15, 2012·Proceedings of the National Academy of Sciences of the United States of America·Alba Di PardoSimonetta Sipione
Dec 4, 2012·Journal of the Neurological Sciences·Jay S SchneiderWei Du
Oct 10, 2013·Brain : a Journal of Neurology·Gaurav V HarlalkaAndrew H Crosby
Nov 15, 2013·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Luis TecedorBeverly L Davidson

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Citations

Apr 11, 2020·International Journal of Molecular Sciences·Bernadette Breiden, Konrad Sandhoff
Nov 5, 2019·Biochimica Et Biophysica Acta. Molecular Basis of Disease·Elisabeth S ButzSusan L Cotman
Jan 1, 2019·Expert Opinion on Orphan Drugs·Jonathan B RosenbergDolan Sondhi
Aug 20, 2021·EMBO Molecular Medicine·Chiara SoldatiDiego L Medina

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Datasets Mentioned

BETA
GM2

Methods Mentioned

BETA
flow cytometry
PCR
Dot Blot
electrophoresis

Software Mentioned

ImageJ

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