Enam, which encodes enamelin, is a gene crucial for the formation of tooth enamel [2,3,4,5,7]. Enamelin is the second most prominent enamel matrix protein, and its production is tightly regulated for the proper formation of mineralized dental tissues like enamel [1]. The gene's function is integral to the process of amelogenesis and enamel biomineralization [1].

In Msx2 mouse mutants, Enam expression is reduced in pre-secretory and secretory ameloblasts. Enam is an early response gene under the control of Msx2, with Msx2 binding to the Enam promoter in vitro and repressing its expression, indicating a spatio-temporal control of Enam by Msx2 [1]. In Enam+/- mice, incisor enamel is thinner with ectopic mineral deposition, and molar enamel can be chalky and rough-surfaced. When combined with Ambn+/- (double heterozygous Enam+/- Ambn+/-), the enamel is thin, rough, and undergoes accelerated attrition due to composite digenic effects [2].

In conclusion, Enam is essential for normal enamel formation. Mouse models, especially those with Enam mutations or altered regulation by Msx2, have revealed its role in amelogenesis and enamel biomineralization. These models also suggest that Enam-related genetic variations can contribute to amelogenesis imperfecta, highlighting its significance in understanding enamel-related diseases [1,2,3,4,5,6,7].

References:

1. Ruspita, Intan, Das, Pragnya, Miyoshi, Keiko, Snead, Malcolm L, Bei, Marianna. 2023. Enam expression is regulated by Msx2. In Developmental dynamics : an official publication of the American Association of Anatomists, 252, 1292-1302. doi:10.1002/dvdy.598. https://pubmed.ncbi.nlm.nih.gov/37191055/

2. Zhang, Hong, Hu, Yuanyuan, Seymen, Figen, Simmer, James P, Hu, Jan C-C. 2019. ENAM mutations and digenic inheritance. In Molecular genetics & genomic medicine, 7, e00928. doi:10.1002/mgg3.928. https://pubmed.ncbi.nlm.nih.gov/31478359/

3. Wang, Y-L, Lin, H-C, Liang, T, Hu, J C-C, Wang, S-K. 2024. ENAM Mutations Can Cause Hypomaturation Amelogenesis Imperfecta. In Journal of dental research, 103, 662-671. doi:10.1177/00220345241236695. https://pubmed.ncbi.nlm.nih.gov/38716742/

4. Yu, Shunlan, Zhang, Chenying, Zhu, Ce, Wang, Xiaozhe, Zheng, Shuguo. 2021. A novel ENAM mutation causes hypoplastic amelogenesis imperfecta. In Oral diseases, 28, 1610-1619. doi:10.1111/odi.13877. https://pubmed.ncbi.nlm.nih.gov/33864320/

5. Crawford, Peter J M, Aldred, Michael, Bloch-Zupan, Agnes. 2007. Amelogenesis imperfecta. In Orphanet journal of rare diseases, 2, 17. doi:. https://pubmed.ncbi.nlm.nih.gov/17408482/

6. Seymen, F, Lee, K-E, Koruyucu, M, Lee, Z H, Kim, J-W. 2014. ENAM mutations with incomplete penetrance. In Journal of dental research, 93, 988-92. doi:10.1177/0022034514548222. https://pubmed.ncbi.nlm.nih.gov/25143514/

7. Martins, Daiana da Silva, Ionta, Franciny Querobim, Pompermaier Garlet, Gustavo, Rios, Daniela, Lussi, Adrian. 2024. Developmental Defects of Enamel. In Monographs in oral science, 32, 10-34. doi:10.1159/000538850. https://pubmed.ncbi.nlm.nih.gov/39321764/