EMBRYONIC TO ADULT CONVERSION OF NEURAL CELL-ADHESION MOLECULES IN NORMAL AND STAGGERER MICE
EMBRYONIC TO ADULT CONVERSION OF NEURAL CELL-ADHESION MOLECULES IN NORMAL AND STAGGERER MICE
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DOI：
10.1073/pnas.79.22.7036
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发表时间：
1982-01-01
期刊：
影响因子：
--
通讯作者：
CHUONG, CM
中科院分区：
文献类型：
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作者：
EDELMAN, GM;CHUONG, CM
神经细胞粘附分子（N-CAM）具有异常高的唾液酸含量（28-35 g/100 g多肽），并且在胚胎或E形态的电泳凝胶中表现出微观异质性。在发育过程中，分子会转化为几种成体或A型，它们类似于E型，但平均只有10%的唾液酸，并且看起来没有微异质性。本研究使用兔抗小鼠N-CAM抗体和2种不同的单克隆抗体来跟踪E .fwdarw。正常小鼠和突变小鼠的转化。E .fwdarw。在野生型小鼠大脑的不同部位，发现了3种形式（Mr[分子比]180,000,Mr 140,000和Mr 120,000）的转换以不同的速率发生。对小鼠颗粒私隐突变株（sg/sg）的整个小脑的检查显示，E .fwdarw。出生后21天还没有发生转换，而在野生型中，这个时候几乎完成了转换。E .fwdarw也有一些延迟。在大脑皮层内sg/sg的转换，尽管在表型上没有发现皮层障碍的证据。在表型正常的幼崽（即sg/ +和+/+的混合物）汇集的组织中，在小脑和皮层也发现了轻微的转化延迟。突变体weaver， reeler和jimpy均表现出正常的E .fwdarw时间表。一个转换。交错突变体的一个主要缺陷可能与N-CAM的局部表面调制失败有关，无法产生分子的A形式。在这种疾病中看到的一些突触形成和细胞存活的失败可能是由异常引起的，这可能改变了N-CAM在发育关键时期的结合特性。
The neural cell adhesion molecule (N-CAM) has an unusually high amount of sialic acid (28-35 g/100 g of polypeptide) and shows microheterogeneity in electrophoretic gels in its embryonic or E form. During development, the molecule undergoes conversion to several adult or A forms, which resemble the E form but which on the average have only 10% sialic acid and do not appear to be microheterogeneous. In the study, rabbit antibodies to mouse N-CAM and 2 different monoclonal antibodies were used to follow the E .fwdarw. A conversion in normal and mutant mice. E .fwdarw. A conversion to 3 forms (Mr [molecular ratio] 180,000, Mr 140,000 and Mr 120,000) was found to occur at different rates in different parts of the brains of wild-type mice. Examination of the entire cerebellum of the granuloprival mouse mutant staggerer (sg/sg) showed that the E .fwdarw. A conversion did not occur by 21 days after birth, whereas in wild type it was almost complete at that time. There was also some delay in E .fwdarw. A conversion within the cerebral cortex of sg/sg, although phenotypically no evidence of cortical disorder was detected. In pooled tissues from phenotypically normal-appearing littermates (i.e., a mixture of sg/ + and +/+), a slight conversion delay was also found in cerebellum and cortex. The mutants weaver, reeler and jimpy all showed normal schedules of E .fwdarw. A conversion. A major defect in staggerer mutants may relate to a failure in local surface modulation of N-CAM to produce the A forms of the molecule. Some of the failures of synapse formation and of cell survival seen in this disease may result from the anomaly, which is likely to alter the binding properties of N-CAM at critical times of development.