MODEL FOR COBALAMIN DEFICIENCY

水果容易导致钴胺(维生素B12、CB1)缺乏 被剥夺了食物来源的蝙蝠(Rousettus Aegyptiacus) 圈养的维他命。他们会患上神经系统疾病 并发症，类似于人类恶性贫血，但 无血液学并发症。这种潜在动物的特征 人类CB1缺乏症的研究模型将沿着 以下是CB1缺陷型和满足型蝙蝠的品系。营养学研究 将扩展到比较CB1、蛋氨酸和胆碱在 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变位酶或蛋氨酸合成酶 与CB1在神经系统中的作用有关的关键酶。这个 CB1缺乏症患者尿液中有机酸的来源和去向 调查，并纳入放射性标记丙酸和 将甲基丙二酸甲酯转化为髓磷脂将在大脑、脊髓中进行测量 和周围神经。CB1的胞内形式的轮廓将是 采用高效液相色谱(HPLC)进行分析。分析 神经系统叶酸将通过高效液相色谱进行测定，并观察其对 叶酸对神经病的影响将被检测。一氧化二氮的影响，一个 假定为CB1拮抗剂，将与纯营养性CB1进行比较 欠缺模型。神经传导研究和感觉诱发电位 将在正常和CB1缺乏的动物身上进行测量。结构研究 将对大脑和脊椎进行髓鞘脂类分析 绳索或蝙蝠，包括圈养出生的小蝙蝠。这个项目寻求 阐明CB1在神经系统组织中的代谢作用及其机制 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.