Tennyson V M, Pham T D, Rothman T P, Gershon M D
Anat Rec. 1986 Jul;215(3):267-81. doi: 10.1002/ar.1092150310.
The terminal portion of the bowel of the lethal spotted mutant mouse (ls/ls) lacks an enteric nervous system due to the failure of neural crest precursors to colonize this region during embryonic life. As a result, the mouse develops congenital megacolon. We have postulated that the defect occurs because the microenvironment of the aganglionic segment is segmentally abnormal and does not permit the migration and/or survival of the enteric neural or glial precursors in the affected zone. We have examined the terminal segment of adult ls/ls and control mice by light and electron microscopy to determine if the defect is associated with identifiable structural abnormalities that persist to maturity. A striking abnormality is an overgrowth of the muscularis mucosa in the adult ls/ls mouse, particularly in the outer longitudinal layer. Electron microscopy also reveals an extensive thickening of the basal lamina around smooth muscle cells. In addition, nerves that are derived from fibers that are extrinsic to this area are abnormal. Large bundles of nerve fibers, some of which contain myelinated axons, large-caliber unmyelinated axons, and abundant collagen, are prominent in the intermuscular region of the aganglionic segments and often reach into the submucosa. The supporting cells of the unmyelinated and myelinated nerves in the aganglionic segment have voluminous perineural cytoplasm typical of immature Schwann cells. They also exhibit intermediate filaments in their cytoplasm. Otherwise they have the typical morphology of peripheral Schwann cells, rather than enteric glia, including individual ensheathment of axons and a surrounding basal lamina. We suggest that the extracellular matrix and/or cells of mesenchymal origin of the terminal bowel of the ls/ls mouse may prevent the ingrowth of the normal precursors of the glia as well as neurons of the enteric nervous system, but may permit or even encourage the ingrowth of abnormal numbers of extrinsic axons.
致死性斑点突变小鼠（ls/ls）肠道的末端部分由于神经嵴前体细胞在胚胎期未能定植到该区域，因而缺乏肠神经系统。结果，该小鼠患上先天性巨结肠。我们推测，这种缺陷的发生是因为无神经节段的微环境存在节段性异常，不允许肠神经或神经胶质前体细胞在受影响区域迁移和/或存活。我们通过光学显微镜和电子显微镜检查了成年ls/ls小鼠和对照小鼠的末端肠段，以确定该缺陷是否与持续到成熟阶段的可识别结构异常有关。一个显著的异常是成年ls/ls小鼠的黏膜肌层过度生长，尤其是在外纵肌层。电子显微镜还显示平滑肌细胞周围的基膜广泛增厚。此外，源自该区域外部纤维的神经也不正常。大束神经纤维在无神经节段的肌间区域很突出，其中一些含有有髓轴突、大口径无髓轴突和丰富的胶原蛋白，并且常常延伸至黏膜下层。无神经节段中无髓和有髓神经的支持细胞具有大量神经周细胞质，这是未成熟雪旺细胞的典型特征。它们的细胞质中还显示有中间丝。除此之外，它们具有外周雪旺细胞而非肠神经胶质细胞的典型形态，包括单个轴突的包绕和周围的基膜。我们认为，ls/ls小鼠末端肠道间充质来源的细胞外基质和/或细胞可能会阻止肠神经系统神经胶质细胞以及神经元的正常前体细胞向内生长，但可能允许甚至促进异常数量的外部轴突向内生长。
