Myoc-KO Mouse

Myoc, also known as myocilin, is a glycoprotein-encoding gene associated with glaucoma pathology. It is involved in the differentiation of mouse osteoblasts and murine gastrocnemius muscle formation, and in C2C12 cells, it promotes differentiation by regulating the TGF-β signaling pathways via CAV1 [3].

Mutations in the MYOC gene are significantly associated with primary open-angle glaucoma (POAG). The penetrance of MYOC mutation in POAG is 60% (95% CI: 51.0% to 68.0%), and in POAG and suspected POAG is 68% (95% CI: 60.0% to 75.0%). Penetrance varies with age, ethnicity, and mutation sites. For example, among Caucasians, Asians, and Africans, the penetrance in POAG is 55%, 71%, 54% respectively, and in POAG and suspected POAG is 64%, 83%, 57% respectively. Some mutation sites show population specificity [1]. Pathogenic MYOC variants are population-associated, and allelic heterogeneity exists in open-angle glaucoma [2]. MYOC was the first identified gene causing POAG [4]. In two Czech families with POAG, pathogenic MYOC variants (c.1099G>A p.(Gly367Arg) and c.1440C>A p.(Asn480Lys)) were found, and carriers of pathogenic variants have a high lifetime risk of developing POAG and often an aggressive disease course [5]. In a Finnish population, the MYOC p.(Gln368Ter) variant was associated with exfoliation glaucoma, primary open-angle glaucoma, overall glaucoma, suspected glaucoma, and glaucoma-related operations [6].

In conclusion, Myoc is crucial in the differentiation of certain cell types and is strongly associated with glaucoma. Studies on Myoc, especially those involving its mutations in different populations, help in understanding the genetic predisposition and penetrance of glaucoma, providing valuable insights for diagnosis, genetic counseling, and potential therapeutic strategies related to glaucoma.

References:

1. Xie, Juan-Juan, Zhang, Guo-Wei, Cui, Hai-Yue, Wang, Shao-Wen, Lu, Hong. 2022. Penetrance of MYOC gene mutation in primary open-angle glaucoma: A systematic review and meta-analysis. In Ophthalmic genetics, 43, 240-247. doi:10.1080/13816810.2021.2021427. https://pubmed.ncbi.nlm.nih.gov/35014583/

2. Liuska, Perttu J, Harju, Mika, Kivelä, Tero T, Turunen, Joni A. 2021. Prevalence of MYOC risk variants for glaucoma in different populations. In Acta ophthalmologica, 99, e1090-e1097. doi:10.1111/aos.14738. https://pubmed.ncbi.nlm.nih.gov/33421356/

3. Zhang, Yuhan, Li, Shuang, Wen, Xin, Li, Shufeng, Yan, Yunqin. 2021. MYOC Promotes the Differentiation of C2C12 Cells by Regulation of the TGF-β Signaling Pathways via CAV1. In Biology, 10, . doi:10.3390/biology10070686. https://pubmed.ncbi.nlm.nih.gov/34356541/

4. Silva, Filipe, Ferreira, Filipa, Faria, Pedro, Girão, Henrique, Pereira, Paulo. 2020. MYOC Gene Sequencing Analysis in Primary Open-Angle Glaucoma Patients from the Centre Region of Portugal. In Acta medica portuguesa, 34, 586-591. doi:10.20344/amp.14922. https://pubmed.ncbi.nlm.nih.gov/33725475/

5. Vergaro, A, Rezková, L, Fichtl, M, Růžičková, E, Lišková, P. . PRIMARY OPEN-ANGLE GLAUCOMA DUE TO MUTATIONS IN THE MYOC GENE. In Ceska a slovenska oftalmologie : casopis Ceske oftalmologicke spolecnosti a Slovenske oftalmologicke spolecnosti, 78, 242-248. doi:10.31348/2022/25. https://pubmed.ncbi.nlm.nih.gov/36220364/

6. Liuska, Perttu J, Lemmelä, Susanna, Havulinna, Aki S, Palotie, Aarno, Turunen, Joni A. . Association of the MYOC p.(Gln368Ter) Variant With Glaucoma in a Finnish Population. In JAMA ophthalmology, 139, 762-768. doi:10.1001/jamaophthalmol.2021.1610. https://pubmed.ncbi.nlm.nih.gov/34081096/