Mice with disrupted GM2/GD2 synthase gene lack complex gangliosides but exhibit only subtle defects in their nervous system - PubMed (original) (raw)
. 1996 Oct 1;93(20):10662-7.
doi: 10.1073/pnas.93.20.10662.
A Yamamoto, K Furukawa, S Yamashiro, M Shin, M Okada, S Fukumoto, M Haraguchi, N Takeda, K Fujimura, M Sakae, M Kishikawa, H Shiku, K Furukawa, S Aizawa
Affiliations
- PMID: 8855236
- PMCID: PMC38211
- DOI: 10.1073/pnas.93.20.10662
Mice with disrupted GM2/GD2 synthase gene lack complex gangliosides but exhibit only subtle defects in their nervous system
K Takamiya et al. Proc Natl Acad Sci U S A. 1996.
Abstract
Gangliosides, sialic acid-containing glycosphingolipids, are abundant in the vertebrate (mammalian) nervous system. Their composition is spatially and developmentally regulated, and gangliosides have been widely believed to lay essential roles in establishment of the nervous system, especially in neuritogenesis and synaptogenesis. However, this has never been tested directly. Here we report the generation of mice with a disrupted beta 1,4-N-acetylgalactosaminyltransferase (GM2/GD2 synthase; EC 2.4.1.92) gene. The mice lacked all complex gangliosides. Nevertheless, they did not show any major histological defects in their nervous systems or in gross behavior. Just a slight reduction in the neural conduction velocity from the tibial nerve to the somatosensory cortex, but not to the lumbar spine, was detected. These findings suggest that complex gangliosides are required in neuronal functions but not in the morphogenesis and organogenesis of the brain. The higher levels of GM3 and GD3 expressed in the brains of these mutant mice may be able to compensate for the lack of complex gangliosides.
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. - A functional role for complex gangliosides: motor deficits in GM2/GD2 synthase knockout mice.
Chiavegatto S, Sun J, Nelson RJ, Schnaar RL. Chiavegatto S, et al. Exp Neurol. 2000 Dec;166(2):227-34. doi: 10.1006/exnr.2000.7504. Exp Neurol. 2000. PMID: 11085888 - 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. - 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 - Disordered testosterone transport in mice lacking the ganglioside GM2/GD2 synthase gene.
Furukawa K, Takamiya K, Ohmi Y, Bhuiyan RH, Tajima O, Furukawa K. Furukawa K, et al. FEBS Open Bio. 2023 Sep;13(9):1615-1624. doi: 10.1002/2211-5463.13603. Epub 2023 Apr 6. FEBS Open Bio. 2023. PMID: 36999634 Free PMC article. Review.
Cited by
- Neurological aspects of human glycosylation disorders.
Freeze HH, Eklund EA, Ng BG, Patterson MC. Freeze HH, et al. Annu Rev Neurosci. 2015 Jul 8;38:105-25. doi: 10.1146/annurev-neuro-071714-034019. Epub 2015 Apr 2. Annu Rev Neurosci. 2015. PMID: 25840006 Free PMC article. Review. - CD4 and CD8 T cells require different membrane gangliosides for activation.
Nagafuku M, Okuyama K, Onimaru Y, Suzuki A, Odagiri Y, Yamashita T, Iwasaki K, Fujiwara M, Takayanagi M, Ohno I, Inokuchi J. Nagafuku M, et al. Proc Natl Acad Sci U S A. 2012 Feb 7;109(6):E336-42. doi: 10.1073/pnas.1114965109. Epub 2012 Jan 17. Proc Natl Acad Sci U S A. 2012. PMID: 22308377 Free PMC article. - Anti-GD2 CAR T cells could prove transformative for H3-K27M+ diffuse midline gliomas.
Furukawa K, Ohmi Y, Furukawa K. Furukawa K, et al. Transl Cancer Res. 2019 Mar;8(Suppl 2):S87-S93. doi: 10.21037/tcr.2018.08.21. Transl Cancer Res. 2019. PMID: 35117070 Free PMC article. No abstract available. - Glycosyltransferases in different brain regions during chick embryo development.
Rizzo AM, Rossi F, Berra B. Rizzo AM, et al. Neurochem Res. 2002 Aug;27(7-8):815-21. doi: 10.1023/a:1020213209078. Neurochem Res. 2002. PMID: 12374218 - Roles of gangliosides in mouse embryogenesis and embryonic stem cell differentiation.
Kwak DH, Seo BB, Chang KT, Choo YK. Kwak DH, et al. Exp Mol Med. 2011 Jul 30;43(7):379-88. doi: 10.3858/emm.2011.43.7.048. Exp Mol Med. 2011. PMID: 21654188 Free PMC article. Review.
References
- Pharmacol Biochem Behav. 1982 Dec;17(6):1251-6 - PubMed
- Cancer Res. 1989 Nov 15;49(22):6258-64 - PubMed
- J Neurosci Res. 1984;12(2-3):245-55 - PubMed
- J Biol Chem. 1989 Oct 25;264(30):17615-8 - PubMed
- Brain Res. 1990 Jan 8;506(2):291-3 - PubMed
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Molecular Biology Databases