MINORITY SCHOOL FACULTY DEVELOPMENT

叶酸参与单碳单位或甲基的转移。 在各种关键的细胞反应中。在人类中，叶酸缺乏 会导致巨幼细胞性贫血和发育性神经畸形。 此外，它还可能使疾病状态复杂化，在那里加速 由于红细胞破坏增加而导致的红细胞生成，如在 镰状细胞性贫血。叶酸缺乏可能会限制营养物质的供应 细胞中甲基化反应的甲基。甲基化是否 与叶酸过程中观察到的无效造血有关 缺乏症尚不清楚。新近发展的镰刀动物模型 与这些疾病非常相似的细胞性贫血和巨幼细胞性贫血 可以帮助回答其中的一些问题。动物们将会是 通过给它们喂以氨基酸为基础的不含叶酸的食物，使它们缺乏叶酸 节食。对甲基化和珠蛋白基因表达的影响可以是 评估过了。 这项建议的具体目标是研究总甲基化能力 DNA甲基化状态及其与珠蛋白基因的关系 表达、珠蛋白链合成率、小鼠和 人镰刀状血红蛋白和红细胞病态。希望这些研究 将有助于更好地了解病理生理学和 叶酸缺乏与镰状细胞病的相互作用。

Folic acid is involved in the transfer of single carbon units or methyl groups in various key cellular reactions. In humans, folate deficiency can lead to megaloblastic anemia and developmental neural malformations. Also it may complicate disease states where there is accelerated erythropoiesis due to an increased destruction of red blood cells, like in sickle cell anemia. Deficiency of folic acid may limit the supply of methyl groups for methylation reactions in the cell. Whether methylation is involved in the ineffective hematopoiesis observed during folate deficiency is not known. The recently developed animal models for sickle cell anemia and megaloblastic anemia which closely resemble these diseases in humans could help answer some of these questions. The animals will be made folate deficient by feeding them an amino acid-based, folate-free diet. The effect on methylation and globin gene expression can be assessed. The specific aims of this proposal are to study total methylation capacity of the cell, methylation status of DNA, and its correlation to globin gene expression, globin chain synthesis rates, relative amounts of mouse and human sickle hemoglobins and erythrocyte sickling. Hopefully these studies will contribute to a better understanding of the pathophysiology and interaction of folate deficiency and sickle cell disease.