Defect of LSS Disrupts Lens Development in Cataractogenesis
Congenital cataract is one of the leading causes of blindness in children worldwide. About one-third of congenital cataracts are caused by genetic defects. LSS, which encodes lanosterol synthase, is a causal gene for congenital cataracts. LSS is critical in preventing abnormal protein aggregation of...
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Frontiers Media S.A.
2021
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oai:doaj.org-article:e5c51601413f4b7e90a22c73a69000372021-12-02T10:52:24ZDefect of LSS Disrupts Lens Development in Cataractogenesis2296-634X10.3389/fcell.2021.788422https://doaj.org/article/e5c51601413f4b7e90a22c73a69000372021-12-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fcell.2021.788422/fullhttps://doaj.org/toc/2296-634XCongenital cataract is one of the leading causes of blindness in children worldwide. About one-third of congenital cataracts are caused by genetic defects. LSS, which encodes lanosterol synthase, is a causal gene for congenital cataracts. LSS is critical in preventing abnormal protein aggregation of various cataract-causing mutant crystallins; however, its roles in lens development remain largely unknown. In our study, we generated a mouse model harboring Lss G589S mutation, which is homologous to cataract-causing G588S mutation in human LSS. LssG589S/G589S mice exhibited neonatal lethality at postal day 0 (P0), whereas these mice showed severe opacity in eye lens. Also, we found that cataract was formed at E17.5 after we examined the opacity of embryonic lens from E13.5 to E18.5. Moreover, disrupted lens differentiation occurred at E14.5 prior to formation of the opacity of eye lens, shown as delayed differentiation of lens secondary fiber and disordered lens fiber organization. In addition, RNA-seq analysis indicated that cholesterol synthesis signaling pathways were significantly downregulated. Overall, our findings provide clear evidence that a mouse model harboring a homozygous Lss G589S mutation can recapitulate human congenital cataract. Our study points out that LSS functions as a critical determinant of lens development, which will contribute to better understanding LSS defects in cataractogenesis and developing therapies for cataracts.Minglei ZhaoTingfang MeiTingfang MeiBizhi ShangBin ZouQing LianQing LianWenchang XuKeling WuYuhua LaiChujun LiuLai WeiJie ZhuKang ZhangYizhi LiuYizhi LiuYizhi LiuLing ZhaoFrontiers Media S.A.articlelanosterol synthasecongenital cataractmouse modelmutationlens developmentBiology (General)QH301-705.5ENFrontiers in Cell and Developmental Biology, Vol 9 (2021) |
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| topic |
lanosterol synthase congenital cataract mouse model mutation lens development Biology (General) QH301-705.5 |
| spellingShingle |
lanosterol synthase congenital cataract mouse model mutation lens development Biology (General) QH301-705.5 Minglei Zhao Tingfang Mei Tingfang Mei Bizhi Shang Bin Zou Qing Lian Qing Lian Wenchang Xu Keling Wu Yuhua Lai Chujun Liu Lai Wei Jie Zhu Kang Zhang Yizhi Liu Yizhi Liu Yizhi Liu Ling Zhao Defect of LSS Disrupts Lens Development in Cataractogenesis |
| description |
Congenital cataract is one of the leading causes of blindness in children worldwide. About one-third of congenital cataracts are caused by genetic defects. LSS, which encodes lanosterol synthase, is a causal gene for congenital cataracts. LSS is critical in preventing abnormal protein aggregation of various cataract-causing mutant crystallins; however, its roles in lens development remain largely unknown. In our study, we generated a mouse model harboring Lss G589S mutation, which is homologous to cataract-causing G588S mutation in human LSS. LssG589S/G589S mice exhibited neonatal lethality at postal day 0 (P0), whereas these mice showed severe opacity in eye lens. Also, we found that cataract was formed at E17.5 after we examined the opacity of embryonic lens from E13.5 to E18.5. Moreover, disrupted lens differentiation occurred at E14.5 prior to formation of the opacity of eye lens, shown as delayed differentiation of lens secondary fiber and disordered lens fiber organization. In addition, RNA-seq analysis indicated that cholesterol synthesis signaling pathways were significantly downregulated. Overall, our findings provide clear evidence that a mouse model harboring a homozygous Lss G589S mutation can recapitulate human congenital cataract. Our study points out that LSS functions as a critical determinant of lens development, which will contribute to better understanding LSS defects in cataractogenesis and developing therapies for cataracts. |
| format |
article |
| author |
Minglei Zhao Tingfang Mei Tingfang Mei Bizhi Shang Bin Zou Qing Lian Qing Lian Wenchang Xu Keling Wu Yuhua Lai Chujun Liu Lai Wei Jie Zhu Kang Zhang Yizhi Liu Yizhi Liu Yizhi Liu Ling Zhao |
| author_facet |
Minglei Zhao Tingfang Mei Tingfang Mei Bizhi Shang Bin Zou Qing Lian Qing Lian Wenchang Xu Keling Wu Yuhua Lai Chujun Liu Lai Wei Jie Zhu Kang Zhang Yizhi Liu Yizhi Liu Yizhi Liu Ling Zhao |
| author_sort |
Minglei Zhao |
| title |
Defect of LSS Disrupts Lens Development in Cataractogenesis |
| title_short |
Defect of LSS Disrupts Lens Development in Cataractogenesis |
| title_full |
Defect of LSS Disrupts Lens Development in Cataractogenesis |
| title_fullStr |
Defect of LSS Disrupts Lens Development in Cataractogenesis |
| title_full_unstemmed |
Defect of LSS Disrupts Lens Development in Cataractogenesis |
| title_sort |
defect of lss disrupts lens development in cataractogenesis |
| publisher |
Frontiers Media S.A. |
| publishDate |
2021 |
| url |
https://doaj.org/article/e5c51601413f4b7e90a22c73a6900037 |
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