Eye Institute, Eye & ENT Hospital of Fudan University, Shanghai, China.
Shanghai Key Laboratory of Visual Impairment and Restoration, Shanghai, China.
Transl Vis Sci Technol. 2024 Jul 1;13(7):11. doi: 10.1167/tvst.13.7.11.
Microphthalmia is a rare developmental eye disease that affects 1 in 7000 births. Currently, there is no cure for this condition. This study aimed to construct a stable mouse model of microphthalmia, thus providing a new tool for the study of the etiology of microphthalmia.
The Hedgehog signaling pathway plays a crucial role in eye development. One of the key mechanisms of the Sonic Hedgehog signaling is the strong transcriptional activation ability of GLI3, a major mediator of this pathway. This study used CRISPR/Cas9 system to construct a novel TgGli3Ki/Ki lens-specific over-expression mouse line. To identify the ocular characteristics of this line, quantitative PCR, Western blot, hematoxylin and eosin staining, immunofluorescent staining, and RNA-seq were performed on the ocular tissues of this line and normal mice.
The TgGli3Ki/Ki lens-specific over-expression mouse model exhibits the ocular phenotype of microphthalmia. In the TgGli3Ki/Ki mouse, Gli3 is over-expressed in the lens, and the size of the eyeball and lens is significantly smaller than the normal one. RNA-seq analysis using the lens and the retina samples from TgGli3Ki/Ki and normal mice indicates that the phototransduction pathway is ectopically activated in the lens. Immunofluorescent staining of the lens samples confirmed this activation.
The TgGli3Ki/Ki mouse model consistently manifests the stereotypical microphthalmia phenotype across generations, making it an excellent tool for studying this severe eye disease.
This study developed a novel animal model to facilitate clinical research on microphthalmia.
小眼症是一种罕见的眼部发育疾病，每 7000 例出生中就有 1 例。目前，这种疾病还没有治愈方法。本研究旨在构建小眼症的稳定小鼠模型，从而为小眼症的病因研究提供新工具。
Hedgehog 信号通路在眼睛发育中起着关键作用。Sonic Hedgehog 信号的一个关键机制是 GLI3 的强转录激活能力，GLI3 是该通路的主要介质。本研究使用 CRISPR/Cas9 系统构建了一种新型的 TgGli3Ki/Ki 晶状体特异性过表达小鼠系。为了鉴定该系的眼部特征，对该系和正常小鼠的眼部组织进行了定量 PCR、Western blot、苏木精和伊红染色、免疫荧光染色和 RNA-seq 分析。
TgGli3Ki/Ki 晶状体特异性过表达小鼠模型表现出小眼症的眼部表型。在 TgGli3Ki/Ki 小鼠中，Gli3 在晶状体中过表达，眼球和晶状体的大小明显小于正常小鼠。使用 TgGli3Ki/Ki 和正常小鼠的晶状体和视网膜样本进行 RNA-seq 分析表明，光转导途径在晶状体中异位激活。晶状体样本的免疫荧光染色证实了这种激活。
TgGli3Ki/Ki 小鼠模型在各世代中一致表现出典型的小眼症表型，是研究这种严重眼部疾病的优秀工具。
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