ENU诱变建立RAX基因无义突变眼畸形小鼠模型

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中图分类号：R771.1；S865.1 文献标志码：A 文章编号：1671-4652（2025）02-0009-07

DOI：10.16872/j.cnki.1671-4652.2025.02.002

ABSTRACT：Theaimof this study wastocreate N-ethyl-N-nitrosourea（ENU）-induced inheritedeye dysmorphologymouse model，and toconduct pathological analysis ofcorneal sectionsforcorneal disease mouse，mapand sequence analysisof thepatho genicgene.Theresultsshowedthatinthecornealmatrixlayer，althoughthecornealstromallayerhadnoblodvessels，itsfiber arrangement were loser，alongwiththepartial absenceof endothelialcels.Andthelocalcornealepithelialcelsof mice with corneal opacityshowed a significant downregulationof Keratin12（K12）signal，while the Keratin14（K14）was expressed most prominently in thecorneal epithelium and was weak in the wild-typecorneal epithelium.These results showed abnormal corneal epithelium diferentiation in mutant corneas.The mutation was mapped to mouse chromosome 18 near maker Dl8Mitl84. The retina and anterior neural fold homeobox （ .RAX） ） was finally selected as a candidate gene for this mutation. On examination of the RAX gene，we found a C/T substitution， in nucleotide position 557 of the RAXcodingregionthatresultedinsubstitutionof anargininecodon（R）byastop（nonsense）codonatposition187，thenprematurely terminated the RAX protein synthesis. This study suggests that the induced RAX gene mutation is expected to establish a new mouse model of eye malformation.

KEY WORDS：mouse；N-ethyl-N-nitrosourea（ENU）；eye dysmorphology；retinaandanteriorneural fold homeobox gene

先天性无眼与小眼畸形（anophthalmia and microphthalmia）属于一种严重的眼球发育异常疾病，新生儿发生率为 0.01%～0.02% ，先天性无眼与小眼畸形一般表现为双侧眼球病变，偶见单侧发病，严重时还伴随有全身综合征。（剩余12639字）