Show simple item record Kuan, CT Chang, J Mansson, JE Li, J Pegram, C Fredman, P McLendon, RE Bigner, DD
dc.coverage.spatial England 2011-06-21T17:29:32Z 2010-11-18
dc.identifier 1471-213X-10-114
dc.identifier.citation BMC Dev Biol, 2010, 10 pp. 114 - ?
dc.description.abstract 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.
dc.format.extent 114 - ?
dc.language ENG
dc.language.iso en_US en_US
dc.relation.ispartof BMC Dev Biol
dc.relation.isversionof 10.1186/1471-213X-10-114
dc.subject Alopecia
dc.subject Amino Acid Sequence
dc.subject Animals
dc.subject B-Lymphocytes
dc.subject Base Sequence
dc.subject Carbohydrate Sequence
dc.subject Embryo, Mammalian
dc.subject Female
dc.subject Gangliosides
dc.subject Immunophenotyping
dc.subject Isoenzymes
dc.subject Male
dc.subject Mice
dc.subject Mice, Inbred C57BL
dc.subject Mice, Knockout
dc.subject Molecular Sequence Data
dc.subject N-Acetylglucosaminyltransferases
dc.subject Obesity
dc.subject Phenotype
dc.subject Reproduction
dc.subject Signal Transduction
dc.subject Spleen
dc.subject Survival Rate
dc.subject Tissue Distribution
dc.title Multiple phenotypic changes in mice after knockout of the B3gnt5 gene, encoding Lc3 synthase--a key enzyme in lacto-neolacto ganglioside synthesis.
dc.title.alternative en_US
dc.type Journal Article
dc.description.version Version of Record en_US 2010-11-18 en_US
duke.description.endpage 114 en_US
duke.description.issue en_US
duke.description.startpage 114 en_US
duke.description.volume 10 en_US
dc.relation.journal Bmc Developmental Biology en_US
pubs.organisational-group /Duke
pubs.organisational-group /Duke/School of Medicine
pubs.organisational-group /Duke/School of Medicine/Clinical Science Departments
pubs.organisational-group /Duke/School of Medicine/Clinical Science Departments/Neurosurgery
pubs.organisational-group /Duke/School of Medicine/Clinical Science Departments/Pathology
pubs.organisational-group /Duke/School of Medicine/Clinical Science Departments/Surgery
pubs.organisational-group /Duke/School of Medicine/Institutes and Centers
pubs.organisational-group /Duke/School of Medicine/Institutes and Centers/Duke Cancer Institute
pubs.publication-status Published online
pubs.volume 10
dc.identifier.eissn 1471-213X

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