Immunohistochemical study on gastroenteric nervous system in trisomy 16 mice:an animal model of Down syndrome

AIM:To study the development of gastroenteric nervous system in trisomy 16 mouse embryos.The gastroenteric nervous system in trisomy 16 mice and their normal littermates, serving as controls from embryonic days 13 to 18 (ED13-18) was identified by using primary antibody against protein gene product (PGP) 9.5.METHODS:Trisomy 16 mouse breeding and trisomy 16 mouse embryos were identified from their normal littermates by chromosome examination; PGP 9.5 immunohistochemical stainning.RESULTS:In normal littermates embryos, the precursor cells from the neural crest migrated into stomach and intestine at ED 13 and ED 14 respectively.Numerous nervous processes connected to each other and formed early nervous networks at ED 14 stomach and ED 15 intestine. Original ganglia in the muscular nervous plexus of the stomach appeared at ED15 with very simple arrangement. At ED 16 the early developed myenteric nervous plexuses were regularly found in the stomach and intestine respectively. In both stomach and intestine, the development of submucosal nervous plexuses were finished at ED17. However, the myenteric nervous plexus and the internal and external submucosal nervous plexuses were differentiated only in the stomach at ED 18.In comparison with the normal littermates, stomach and intestine nervous system developed much slower in trisomy 16 mice. Their immature neurons did not appear in the stomach and intestine until ED 14 and ED 15. Between ED 14 and ED 16, the gastroenteric nervous system was composed of only some scattered neurons with different distribution density and size. The development and differentiation of the gastroenteric nervous system were delayed and the myenteric nervous plexus did not appear until ED 18. There was no submucosal nervous plexus in all stomach and intestine specimens. A semiquantitative analysis and rank sum test of the data showed that the trisomy 16 mouse embryos were markedly retarded in the gastroenteric nervous development compared with their normal littermates.CONCLUSION:Trisomy 16 mice, as an animal model for Down syndrome, has abnormality not only in several systems and organs but also in gastroenteric innervation. This report describes for the first time that the development of the gastroenteric nervous system was not only delayed but also pathological.