A functional role for complex gangliosides: motor deficits in GM2/GD2 synthase knockout mice - PubMed (original) (raw)
. 2000 Dec;166(2):227-34.
doi: 10.1006/exnr.2000.7504.
Affiliations
- PMID: 11085888
- DOI: 10.1006/exnr.2000.7504
Free article
A functional role for complex gangliosides: motor deficits in GM2/GD2 synthase knockout mice
S Chiavegatto et al. Exp Neurol. 2000 Dec.
Free article
Abstract
Although gangliosides are abundant molecular determinants on all vertebrate nerve cells (comprising approximately 1.5% of brain dry weight) their functions have remained obscure. We report that mice engineered to lack a key enzyme in complex ganglioside biosynthesis (GM2/GD2 synthase), and which express only the simple ganglioside molecular species GM3 and GD3, develop significant and progressive behavioral neuropathies, including deficits in reflexes, strength, coordination, and balance. Quantitative indices of motor abilities, applied at 8 and 12 months of age, also revealed progressive gait disorders in complex ganglioside knockout mice compared to controls, including reduced stride length, stride width, and increased hindpaw print length as well as a marked reduction in rearing. Compared to controls, null mutant mice tended to walk in small labored movements. Twelve-month-old complex ganglioside knockout mice also displayed significant incidence of tremor and catalepsy. These comprehensive neurobehavioral studies establish an essential role for complex gangliosides in the maintenance of normal neural physiology in mice, consistent with a role in maintaining axons and myelin (Sheikh, K. A. , J. Sun, Y. Liu, H. Kawai, T. O. Crawford, R. L. Proia, J. W. Griffin, and R. L. Schnaar. 1999. Mice lacking complex gangliosides develop Wallerian degeneration and myelination defects. Proc. Natl. Acad. Sci. USA 96: 7532-7537), and may provide insights into the mechanisms underlying certain neural degenerative diseases.
Copyright 2000 Academic Press.
Similar articles
- Mice lacking complex gangliosides develop Wallerian degeneration and myelination defects.
Sheikh KA, Sun J, Liu Y, Kawai H, Crawford TO, Proia RL, Griffin JW, Schnaar RL. Sheikh KA, et al. Proc Natl Acad Sci U S A. 1999 Jun 22;96(13):7532-7. doi: 10.1073/pnas.96.13.7532. Proc Natl Acad Sci U S A. 1999. PMID: 10377449 Free PMC article. - Neuromuscular synaptic transmission in aged ganglioside-deficient mice.
Zitman FM, Todorov B, Verschuuren JJ, Jacobs BC, Furukawa K, Furukawa K, Willison HJ, Plomp JJ. Zitman FM, et al. Neurobiol Aging. 2011 Jan;32(1):157-67. doi: 10.1016/j.neurobiolaging.2009.01.007. Epub 2009 Feb 23. Neurobiol Aging. 2011. PMID: 19233512 - Reduced motor and sensory functions and emotional response in GM3-only mice: emergence from early stage of life and exacerbation with aging.
Tajima O, Egashira N, Ohmi Y, Fukue Y, Mishima K, Iwasaki K, Fujiwara M, Inokuchi J, Sugiura Y, Furukawa K, Furukawa K. Tajima O, et al. Behav Brain Res. 2009 Mar 2;198(1):74-82. doi: 10.1016/j.bbr.2008.10.024. Epub 2008 Nov 1. Behav Brain Res. 2009. PMID: 19013484 - [Functional analysis of the nervous system in knockout mice of ganglioside synthase genes].
Furukawa K, Sugiura Y, Tajima O, Honda T, Furukawa K. Furukawa K, et al. Tanpakushitsu Kakusan Koso. 2004 Nov;49(15 Suppl):2411-6. Tanpakushitsu Kakusan Koso. 2004. PMID: 15552994 Review. Japanese. No abstract available. - Beta1,4-N-acetylgalactosaminyltransferase--GM2/GD2 synthase: a key enzyme to control the synthesis of brain-enriched complex gangliosides.
Furukawa K, Takamiya K, Furukawa K. Furukawa K, et al. Biochim Biophys Acta. 2002 Dec 19;1573(3):356-62. doi: 10.1016/s0304-4165(02)00403-8. Biochim Biophys Acta. 2002. PMID: 12417418 Review.
Cited by
- It's a lipid's world: bioactive lipid metabolism and signaling in neural stem cell differentiation.
Bieberich E. Bieberich E. Neurochem Res. 2012 Jun;37(6):1208-29. doi: 10.1007/s11064-011-0698-5. Epub 2012 Jan 14. Neurochem Res. 2012. PMID: 22246226 Free PMC article. Review. - Functional roles of gangliosides in neurodevelopment: an overview of recent advances.
Yu RK, Tsai YT, Ariga T. Yu RK, et al. Neurochem Res. 2012 Jun;37(6):1230-44. doi: 10.1007/s11064-012-0744-y. Epub 2012 Mar 13. Neurochem Res. 2012. PMID: 22410735 Free PMC article. Review. - Glycosphingolipid functions: insights from engineered mouse models.
Proia RL. Proia RL. Philos Trans R Soc Lond B Biol Sci. 2003 May 29;358(1433):879-83. doi: 10.1098/rstb.2003.1268. Philos Trans R Soc Lond B Biol Sci. 2003. PMID: 12803921 Free PMC article. Review. - Human genetic disorders of sphingolipid biosynthesis.
Astudillo L, Sabourdy F, Therville N, Bode H, Ségui B, Andrieu-Abadie N, Hornemann T, Levade T. Astudillo L, et al. J Inherit Metab Dis. 2015 Jan;38(1):65-76. doi: 10.1007/s10545-014-9736-1. Epub 2014 Aug 21. J Inherit Metab Dis. 2015. PMID: 25141825 Review. - Disease-modifying effects of ganglioside GM1 in Huntington's disease models.
Alpaugh M, Galleguillos D, Forero J, Morales LC, Lackey SW, Kar P, Di Pardo A, Holt A, Kerr BJ, Todd KG, Baker GB, Fouad K, Sipione S. Alpaugh M, et al. EMBO Mol Med. 2017 Nov;9(11):1537-1557. doi: 10.15252/emmm.201707763. EMBO Mol Med. 2017. PMID: 28993428 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Molecular Biology Databases