Chst5-KO Mouse

Chst5, also known as carbohydrate (N-acetylglucosamine-6-O) sulfotransferase 5, encodes an N-acetylglucosamine-6-O-sulfotransferase integral to the sulfation of keratan sulfate (KS) chains. KS is a glycosaminoglycan important for matrix assembly and homeostasis in collagen-rich tissues. Chst5 is involved in processes like myogenesis and may play a role in goblet cell function modulation related to mucosal barrier function [3,4,5,6,8]. Gene expression studies in different cell and tissue models help understand its functions [3,4,5,6,8].

In Chst5-null mouse models, the corneas were significantly thinner, lacked high-sulfated KS, and had abnormal chondroitin sulfate/dermatan sulfate PG complexes and altered collagen fibrillar architecture, indicating its importance in corneal matrix morphogenesis [2,7]. Selective knockdown of wild-type Chst5 in mouse corneal endothelium induced experimental macular corneal dystrophy (MCD), similar to human MCD patients, and mice with Chst5 point mutation recapitulated MCD phenotypes, highlighting its role in MCD development [1]. In myogenesis, inactivation of Chst5 by specific shRNA in murine satellite cells delayed their fusion [5].

In conclusion, Chst5 is crucial for KS biosynthesis, which is essential for matrix organization in tissues like the cornea. Mouse models, especially Chst5-null and knockdown models, have revealed its significant role in corneal-related diseases like MCD and in myogenesis. Understanding Chst5 function provides insights into these biological processes and potential therapeutic targets for associated diseases.

References:

1. Zhang, Bi-Ning, Qi, Benxiang, Dong, Chunxiao, Zhou, Qingjun, Xie, Lixin. 2023. The role of corneal endothelium in macular corneal dystrophy development and recurrence. In Science China. Life sciences, 67, 332-344. doi:10.1007/s11427-023-2364-3. https://pubmed.ncbi.nlm.nih.gov/37480470/

2. Parfitt, Geraint J, Pinali, Christian, Akama, Tomoya O, Quantock, Andrew J, Knupp, Carlo. 2011. Electron tomography reveals multiple self-association of chondroitin sulphate/dermatan sulphate proteoglycans in Chst5-null mouse corneas. In Journal of structural biology, 174, 536-41. doi:10.1016/j.jsb.2011.03.015. https://pubmed.ncbi.nlm.nih.gov/21440637/

3. Bhatia, Shikha, Prabhu, P Nagendra, Benefiel, Ann C, Davis, Steven R, Gaskins, H Rex. 2014. Galacto-oligosaccharides may directly enhance intestinal barrier function through the modulation of goblet cells. In Molecular nutrition & food research, 59, 566-73. doi:10.1002/mnfr.201400639. https://pubmed.ncbi.nlm.nih.gov/25421108/

4. Yao, Qianqian, Li, Huiying, Gao, Yanan, Delcenserie, Véronique, Wang, Jiaqi. 2023. The Milk Active Ingredient, 2'-Fucosyllactose, Inhibits Inflammation and Promotes MUC2 Secretion in LS174T Goblet Cells In Vitro. In Foods (Basel, Switzerland), 12, . doi:10.3390/foods12010186. https://pubmed.ncbi.nlm.nih.gov/36613400/

5. Grassot, Vincent, Da Silva, Anne, Saliba, James, Dupuy, Fabrice, Petit, Jean-Michel. 2014. Highlights of glycosylation and adhesion related genes involved in myogenesis. In BMC genomics, 15, 621. doi:10.1186/1471-2164-15-621. https://pubmed.ncbi.nlm.nih.gov/25051993/

6. Cheng, Lianghui, Kong, Chunli, Walvoort, Marthe T C, Faas, Marijke M, de Vos, Paul. 2019. Human Milk Oligosaccharides Differently Modulate Goblet Cells Under Homeostatic, Proinflammatory Conditions and ER Stress. In Molecular nutrition & food research, 64, e1900976. doi:10.1002/mnfr.201900976. https://pubmed.ncbi.nlm.nih.gov/31800974/

7. Hayashida, Yasutaka, Akama, Tomoya O, Beecher, Nicola, Nishida, Kohji, Quantock, Andrew J. 2006. Matrix morphogenesis in cornea is mediated by the modification of keratan sulfate by GlcNAc 6-O-sulfotransferase. In Proceedings of the National Academy of Sciences of the United States of America, 103, 13333-8. doi:. https://pubmed.ncbi.nlm.nih.gov/16938851/

8. Ren, Chengcheng, Dokter-Fokkens, Jelleke, Figueroa Lozano, Susana, Faas, Marijke M, de Vos, Paul. 2019. Fibroblasts Impact Goblet Cell Responses to Lactic Acid Bacteria After Exposure to Inflammatory Cytokines and Mucus Disruptors. In Molecular nutrition & food research, 63, e1801427. doi:10.1002/mnfr.201801427. https://pubmed.ncbi.nlm.nih.gov/30977971/