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- Kuan, Chien-Tsun (author)
Multiple phenotypic changes in mice after knockout of the B3gnt5 gene, encoding Lc3 synthase-a key enzyme in lacto-neolacto ganglioside synthesis
- Article/chapterEnglish2010
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- 2010
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- LIBRIS-ID:oai:gup.ub.gu.se/140009
- https://gup.ub.gu.se/publication/140009URI
- https://doi.org/10.1186/1471-213X-10-114DOI
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- Language:English
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- Background Ganglioside biosynthesis occurs through a multi-enzymatic pathway which at the lactosylceramide step is branched into several biosynthetic series. Lc3 synthase utilizes a variety of galactose-terminated glycolipids as acceptors by establishing a glycosidic bond in the beta-1,3-linkage to GlcNaAc to extend the lacto- and neolacto-series gangliosides. In order to examine the lacto-series ganglioside functions in mice, we used gene knockout technology to generate Lc3 synthase gene B3gnt5-deficient mice by two different strategies and compared the phenotypes of the two null mouse groups with each other and with their wild-type counterparts. Results B3gnt5 gene knockout mutant mice appeared normal in the embryonic stage and, if they survived delivery, remained normal during early life. However, about 9% developed early-stage growth retardation, 11% died postnatally in less than 2 months, and adults tended to die in 5-15 months, demonstrating splenomegaly and notably enlarged lymph nodes. Without lacto-neolacto series gangliosides, both homozygous and heterozygous mice gradually displayed fur loss or obesity, and breeding mice demonstrated reproductive defects. Furthermore, B3gnt5 gene knockout disrupted the functional integrity of B cells, as manifested by a decrease in B-cell numbers in the spleen, germinal center disappearance, and less efficiency to proliferate in hybridoma fusion. Conclusions These novel results demonstrate unequivocally that lacto-neolacto series gangliosides are essential to multiple physiological functions, especially the control of reproductive output, and spleen B-cell abnormality. We also report the generation of anti-IgG response against the lacto-series gangliosides 3'-isoLM1 and 3',6'-isoLD1.
Subject headings and genre
- MEDICIN OCH HÄLSOVETENSKAP Medicinska och farmaceutiska grundvetenskaper Neurovetenskaper hsv//swe
- MEDICAL AND HEALTH SCIENCES Basic Medicine Neurosciences hsv//eng
- myelin-associated glycoprotein
- nervous-system
- in-vivo
- lactotetraose series
- gm3
- antibodies
- glycosphingolipids
- model
- brain
- regeneration
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- Chang, Jinli (author)
- Månsson, Jan-Eric,1946Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry(Swepub:gu)xmanja (author)
- Li, Jianjun (author)
- Pegram, Charles (author)
- Fredman, Pam,1950Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry(Swepub:gu)xfredp (author)
- McLendon, Roger E. (author)
- Bigner, Darell D. (author)
- Göteborgs universitetInstitutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi (creator_code:org_t)
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- In:BMC Developmental Biology101471-213X
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