title: Conditional LoxP-flanked glucosylceramide synthase allele controlling glycosphingolipid synthesis.
abstract: Glycosphingolipids are organizational building blocks of plasma membranes that participate in key cellular functions, such as signaling and cell-to-cell interactions. Glucosylceramide synthase--encoded by the Ugcg gene--controls the first committed step in the major pathway of glycosphingolipid synthesis. Global disruption of the Ugcg gene in mice is lethal during gastrulation. We have now established a Ugcg allele flanked by loxP sites (floxed). When cre recombinase was expressed in the nervous system under control of the nestin promoter, the floxed gene underwent recombination, resulting in a substantial reduction of Ugcg expression and of glycosphingolipid ganglio-series levels. The mice deficient in Ugcg expression in the nervous system show a striking loss of Purkinje cells and abnormal neurologic behavior. The floxed Ugcg allele will facilitate analysis of the function of glycosphingolipids in development, physiology, and in diseases such as diabetes and cancer.
authors.affiliation: Genetics of Development and Disease Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Tadashi
authors.initials: T
authors.lastname: Yamashita
authors.forename: Maria Laura
authors.initials: ML
authors.lastname: Allende
authors.forename: Danielle N
authors.initials: DN
authors.lastname: Kalkofen
authors.forename: Norbert
authors.initials: N
authors.lastname: Werth
authors.forename: Konrad
authors.initials: K
authors.lastname: Sandhoff
authors.forename: Richard L
authors.initials: RL
authors.lastname: Proia
mesh_terms: D000483:Alleles; D000818:Animals; D001522:Behavior, Animal; D001921:Brain / Q000378:metabolism*; D003433:Crosses, Genetic; D005964:Glucosyltransferases / Q000096:biosynthesis / Q000235:genetics*; D006028:Glycosphingolipids / Q000096:biosynthesis*; D019426:Integrases / Q000096:biosynthesis / Q000235:genetics; D007381:Intermediate Filament Proteins / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000235:genetics; D064231:Nestin; D011401:Promoter Regions, Genetic; D011689:Purkinje Cells / Q000166:cytology / Q000378:metabolism; D011995:Recombination, Genetic
chemical_list: D006028:Glycosphingolipids; D007381:Intermediate Filament Proteins; D009419:Nerve Tissue Proteins; C577485:Nes protein, mouse; D064231:Nestin; D005964:Glucosyltransferases; C023246:ceramide glucosyltransferase; C045073:Cre recombinase; D019426:Integrases