Open Access

Mutated SASH1 promotes Mitf expression in a heterozygous mutated SASH1 knock‑in mouse model

  • Authors:
    • Zexi Xu
    • Yadong Li
    • Dahong Wang
    • Daoqiu Wu
    • Jinyun Wang
    • Lian Chen
    • Yinqian Deng
    • Jing Zhang
    • Zhixiong Wu
    • Xin Wan
    • Qianfan Liu
    • Hai Huang
    • Pingsheng Hu
    • Jiawei Zeng
    • Ding'an Zhou
  • View Affiliations

  • Published online on: June 19, 2020     https://doi.org/10.3892/ijmm.2020.4652
  • Pages: 1118-1134
  • Copyright: © Xu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

The SAM and SH3 domain‑containing 1 (SASH1) genes have been identified as the causal genes of dyschromatosis universalis hereditaria (DUH); these genes cause the pathological phenotypes of DUH, and SASH1 variants have been shown to regulate the abnormal pigmentation phenotype in human skin in various genodermatoses. However, investigations into the mutated SASH1 gene have been limited to in vitro studies. In the present study, to recapitulate the molecular pathological phenotypes of individuals with DUH induced by SASH1 mutations, a heterozygous BALB/c mouse model, in which the human SASH1 c.1654 T>G (p. Tyr 551Asp, Y551D) mutation was knocked in was first generated. The in vivo functional experiments on Y551D SASH1 indicated that the increased expression of microphthalmia‑associated transcription factor (Mitf) was uniformly induced in the tails of heterozygous BALB/c mice, and an increased quantity of Mitf‑positive epithelial cells was also detected. An increased expression of Mitf‑ and Mitf‑positive cells was also demonstrated in the epithelial tissues of Y551D‑SASH1 affected individuals. In the present study, Mitf expression was also found to be increased by Y551D SASH1 in vitro. Taken together, these findings indicate that the upregulation of Mitf is the bona fide effector of the Y551D SASH1‑mediated melanogenesis signaling pathway in vivo. SASH1 may function as a scaffold molecule for the assembly of a SASH1‑Mitf molecular complex to regulate Mitf expression in the cell nucleus and thus to promote the hyperpigmented phenotype in the pathogenesis of DUH and other genodermatoses related to pigment abnormalities.

Related Articles

Journal Cover

September-2020
Volume 46 Issue 3

Print ISSN: 1107-3756
Online ISSN:1791-244X

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
Spandidos Publications style
Xu Z, Li Y, Wang D, Wu D, Wang J, Chen L, Deng Y, Zhang J, Wu Z, Wan X, Wan X, et al: Mutated SASH1 promotes Mitf expression in a heterozygous mutated SASH1 knock‑in mouse model. Int J Mol Med 46: 1118-1134, 2020
APA
Xu, Z., Li, Y., Wang, D., Wu, D., Wang, J., Chen, L. ... Zhou, D. (2020). Mutated SASH1 promotes Mitf expression in a heterozygous mutated SASH1 knock‑in mouse model. International Journal of Molecular Medicine, 46, 1118-1134. https://doi.org/10.3892/ijmm.2020.4652
MLA
Xu, Z., Li, Y., Wang, D., Wu, D., Wang, J., Chen, L., Deng, Y., Zhang, J., Wu, Z., Wan, X., Liu, Q., Huang, H., Hu, P., Zeng, J., Zhou, D."Mutated SASH1 promotes Mitf expression in a heterozygous mutated SASH1 knock‑in mouse model". International Journal of Molecular Medicine 46.3 (2020): 1118-1134.
Chicago
Xu, Z., Li, Y., Wang, D., Wu, D., Wang, J., Chen, L., Deng, Y., Zhang, J., Wu, Z., Wan, X., Liu, Q., Huang, H., Hu, P., Zeng, J., Zhou, D."Mutated SASH1 promotes Mitf expression in a heterozygous mutated SASH1 knock‑in mouse model". International Journal of Molecular Medicine 46, no. 3 (2020): 1118-1134. https://doi.org/10.3892/ijmm.2020.4652