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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. The inventors have 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 sphingo-lipid behavior.
The Research Tools available are mice with a floxed Ugcg allele that can be deleted in a conditional manner. These mice carrying floxed Ugcg alleles will be useful for delineating the functional roles of glycosphingolipid synthesis in the nervous system and in other physiologic systems.
- Study of the functional roles of glycosphingolipid synthesis in the nervous system and other physiologic systems.
- The floxed Ugcg allele will facilitate analysis of the function of glycosphingolipids in development, physiology, and in diseases such as diabetes and cancer.