MODEL FOR COBALAMIN DEFICIENCY

钴胺素（维生素B12，Cb1）缺乏可以很容易地诱导水果 蝙蝠（Rousettus aegyptiacus）被剥夺了食物来源， 维生素在圈养。 他们会患上一种神经系统疾病 并发症，类似于在人类恶性贫血中看到的并发症，但 没有血液并发症。 这种潜在动物的特征 将沿着进一步研究用于研究人类Cb 1缺乏症的模型 cb1缺乏和cb1充足的蝙蝠中的以下线条。 营养研究 将扩展到比较cb1，蛋氨酸和胆碱的影响， 防止神经系统的变化 将进行生化研究 以评估甲基丙二酰辅酶A β或蛋氨酸合成酶是否 与cb1在神经系统中的作用有关的关键酶。 的 在cb1缺乏症患者尿液中发现的有机酸的来源和归宿将被 研究，并掺入放射性标记的丙酸盐和 将在脑、脊髓和脊髓中测量甲基丙二酸盐转化为髓鞘脂质的能力。 和外周神经。 cb1的细胞内形式的分布将是 使用高效液相色谱法（HPLC）分析。 分析 神经系统叶酸将进行hplc和影响 将测试叶酸对神经病变的影响。 一氧化二氮的影响， 假定的cb1拮抗剂，将与纯营养cb1进行比较 缺陷模型 神经传导检查和感觉诱发电位 将在正常和CB 1缺陷动物中测量。 结构研究 髓鞘脂质分析将在大脑和脊髓中进行， 绳或蝙蝠，包括在圈养出生的年轻蝙蝠。 项目的目标是 为了阐明cb1在神经系统组织中的代谢作用， 与其他营养素的相互作用，特别是蛋氨酸和叶酸。

Cobalamin (vitamin B12, Cb1) deficiency can be readily induced in fruit bats (Rousettus aegyptiacus) which are deprived of a dietary source of the vitamin in captivity. They develop an illness with neurological complications, resembling those seen in human pernicious anemia, but without hematological complications. The features of this potential animal model for study of human Cb1 deficiency will be further investigated along the following lines in cb1-deficient and replete bats. Nutritional studies will be extended to compare the effects of cb1, methionine and choline in preventing the neurological changes. Biochemical studies will be carried out to assess whether methylmalonyl CoA mutase or methionine synthetase is the key enzyme in relation to the role of cb1 in the nervous system. The origin and fate of organic acids found in urine in cb1 deficiency will be investigated, and the incorporation of radiolabelled propionate and methylmalonate into myelin lipids will be measured in brain, spinal cord and peripheral nerves. The profile of intracellular forms of cb1 will be analyzed using high performance liquid chromatographpy (hplc). Analysis of nervous system folates will be carried out by hplc and the effects of folate on the neuropathy will be tested. The effects of nitrous oxide, a putative cb1 antagonist, will be compared with the pure nutritional cb1 deficient model. Nerve conduction studies and sensory evoked potentials will be measured in normal and cb1 deficient animals. Structural studies and myelin lipid analysis will be carried out on the brains and spinal cords or bats, including young bats born in captivity. This project seeks to elucidate the metabolic role of cb1 in nervous system tissue and its interaction with other nutrients, notably methionine and folate.