The Knockout of the Mouse Muc5ac

小鼠 Muc5ac 的敲除

• 批准号: 8149103
• 负责人: Robert Langenbach
• 金额: $ 32.43万
• 依托单位: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8149103
• 关键词: Knockout Mice

The successful knockout of Muc5ac has been achieved and was verified by genomic Southern and PCR analysis. The homozygous Muc5ac-/- mice had significantly reduced levels of mucus on the surface of the gastric mucosa and in the gastric pit compared to wild type mice. In addition, the middle ear of the Muc5ac-/- animals contain smaller goblet cells with decreased mucous content compared to wild type mice. In addition, mononuclear inflammatory cell infiltration was observed in the lamina propria of the middle ear of the Muc5ac-/- mice, which would makes the epithelium more susceptible to bacterial invasion. The conjunctiva and nasopharynx of the Muc5ac-/- mice also have significantly fewer and smaller goblet cells which contain decreased amount of mucous. The protective role of Muc5ac in the stomach was evaluated by the oral dosing of Muc5ac wildtype and deficient mice with indomethacin (indo), a non-steroidal anti-inflammatory drug known to produce gastric ulcers. At various times after acute dosing the stomachs were examined for gastritis and ulceration. The results indicated that Muc5ac deficiency increased the susceptibility to indo-induced gastritis and ulcer formation as indicated by both the number and size of the gastric lesions. Furthermore, histological examination also showed that the severity of gastric lesion erosion was greater in Muc5ac-/- mice. Future investigations will continue to investigate the levels of gastritis and ulceration in NSAID treated Muc5ac-/- mice. In addition, in collaboration with Dr. Stavros Garantziotis we will examine the roles of Muc5ac in pulmonary inflammation and airflow obstruction using a mouse asthma model.

MUC5AC的成功敲除已经实现，并通过基因组南部和PCR分析得到了验证。与野生型小鼠相比，纯合MUC5AC - / - 小鼠在胃粘膜表面和胃坑的表面上的粘液水平明显降低。 此外，与野生型小鼠相比，MUC5AC - / - 动物的中耳动物中的含有粘液含量降低的杯状细胞。此外，在MUC5AC - / - 小鼠中耳的椎板上观察到单核炎症细胞浸润，这会使上皮更容易受到细菌侵袭的影响。 MUC5AC - / - 小鼠的结膜和鼻咽的结膜和鼻咽也明显较少和较小的杯状细胞，含有粘液量降低。 MUC5AC在胃中的保护作用通过MUC5AC野生型的口服剂量和用吲哚美辛（Indo）（一种非甾体类抗炎药）的口服剂量评估。在急性给药后的不同时间检查胃炎和溃疡。结果表明，MUC5AC缺乏提高了对印度胃炎和溃疡形成的敏感性，如胃病变的数量和大小所示。此外，组织学检查还表明，MUC5AC - / - 小鼠的胃病变侵蚀的严重程度更大。未来的研究将继续研究NSAID治疗的MUC5AC - / - 小鼠的胃炎水平和溃疡。此外，与Stavros Garantziotis博士合作，我们将使用小鼠哮喘模型研究MUC5AC在肺部炎症和气流阻塞中的作用。