Multiple phenotypic changes in mice after knockout of the B3gnt5 gene, encoding Lc3 synthase--a key enzyme in lacto-neolacto ganglioside synthesis.
| dc.contributor.author | Kuan, Chien-Tsun | |
| dc.contributor.author | Chang, Jinli | |
| dc.contributor.author | Mansson, Jan-Eric | |
| dc.contributor.author | Li, Jianjun | |
| dc.contributor.author | Pegram, Charles | |
| dc.contributor.author | Fredman, Pam | |
| dc.contributor.author | McLendon, Roger E | |
| dc.contributor.author | Bigner, Darell D | |
| dc.coverage.spatial | England | |
| dc.date.accessioned | 2011-06-21T17:29:32Z | |
| dc.date.issued | 2010-11-18 | |
| 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.description.version | Version of Record | |
| dc.identifier | ||
| dc.identifier | 1471-213X-10-114 | |
| dc.identifier.eissn | 1471-213X | |
| dc.identifier.uri | ||
| dc.language | eng | |
| dc.language.iso | en_US | |
| dc.publisher | Springer Science and Business Media LLC | |
| dc.relation.ispartof | BMC Dev Biol | |
| dc.relation.isversionof | 10.1186/1471-213X-10-114 | |
| dc.relation.journal | Bmc Developmental Biology | |
| 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 | ||
| dc.type | Journal article | |
| duke.contributor.orcid | McLendon, Roger E|0000-0001-6682-4588 | |
| duke.contributor.orcid | Bigner, Darell D|0000-0001-5548-4899 | |
| duke.date.pubdate | 2010-11-18 | |
| duke.description.issue | ||
| duke.description.volume | 10 | |
| pubs.author-url | ||
| pubs.begin-page | 114 | |
| pubs.organisational-group | Clinical Science Departments | |
| pubs.organisational-group | Duke | |
| pubs.organisational-group | Duke Cancer Institute | |
| pubs.organisational-group | Institutes and Centers | |
| pubs.organisational-group | Neurosurgery | |
| pubs.organisational-group | Pathology | |
| pubs.organisational-group | School of Medicine | |
| pubs.organisational-group | Surgery | |
| pubs.publication-status | Published online | |
| pubs.volume | 10 |