REGULATION OF GLOBOPENTOSYLCERAMIDE EXPRESSION

描述（改编自申请人的描述）：糖脂是细胞 由不同的碳水化合物结构组成的表面分子 连接到神经酰胺骨架上。 大量证据表明， 这些分子在组织发育和细胞生长中起作用。 分化 然而，糖脂在细胞中的确切作用 发育生物学也是未知的。 此外，调控因素 发育过程中糖脂的表达尚未阐明。 本提案中的研究涉及以下方面的发育调控： 球戊糖神经酰胺（GbO 5）表达。 这种糖脂被表达为 在小鼠胎盘、睾丸发育过程中的特定时间， 卵巢，并已被建议在其发展中发挥作用。 此外，这种糖脂是一种状态的标志物， 成年小鼠中某些细胞类型的分化。 为了研究GbO 5基因表达的发育规律， 这种糖脂在分化中的作用，即GbO 5合成酶 （N-乙酰氨基半乳糖转移酶）将被纯化，并且其氨基酸 序列将被确定。 编码GbO 5合成酶的基因将被 分离和克隆。 Gb 05基因的时空调控 然后将研究鼠发育期间的表达， 免疫组织化学研究证实。 未来的研究将通过操纵GbO 5的结果进行调查 在培养的细胞系中表达，并最终在转基因小鼠中表达 模型 GbO 5表达可作为调控的模型， 糖脂表达的功能。 因此，研究 本建议中概述的内容可能会增强我们对以下作用的理解， 糖脂在发育和分化中起作用。

DESCRIPTION (Adapted from Applicant's Description): Glycolipids are cell surface molecules which consist of distinct carbohydrate structures attached to a ceramide backbone. Considerable evidence suggests that these molecules play a role in tissue development and cellular differentiation. However, the precise role of glycolipids in cellular and developmental biology is unknown. Moreover, factors which regulate glycolipid expression during development have not been elucidated. The studies in this proposal address the developmental regulation of globopentosylceramide (GbO5) expression. This glycolipid is expressed at specific times during the development of mouse placenta, testis, and ovaries, and has been suggested to play a role in their development. Additionally, this glycolipid is a marker for the state of differentiation of some cell types in adult mice. In order to study the developmental regulation of GbO5 expression and the role of this glycolipid in differentiation, the enzyme GbO5 synthetase (N-acetylgalactosaminyltransferase) will be purified and its amino acid sequence will be determined. The gene encoding GbO5 synthetase will be isolated and cloned. The temporal and spatial regulation of Gb05 gene expression during murine development will then be investigated and corroborated with immunohistochemical studies. Future studies will be investigated by the results of manipulating GbO5 expression in cultured cell lines, and eventually in a transgenic mouse model. GbO5 expression may serve as a model for the regulation and function of glycolipid expression in general. Thus, the studies outlined in this proposal may enhance our understanding of the role that glycolipids play in development and differentiation.