Hepsin Expression: The Key To Unlocking Genetically Inhibited Auditory Function

    The ways in which humans process their environment are dependent on the functionality of our five senses: taste, touch, vision, smell, and hearing. For some people, the ability to process a specific stimulus is inhibited through genetic variations of gene expression and alters the reality of their day to day lives. Auditory processing is a crucial way in which we communicate and express our thoughts, feelings, and ideas as well as forming the awareness of the situation presented to us. In an effort to restore this function to people with inhibited auditory function, researchers have looked to the gene expression of type II trans-membrane serine proteases (TMPRSS), specifically TMPRSS 1 and 3, and their role in hereditary deafness. 

    During a session of Loyola's Neuroscience Seminar, Dr.Wei-Ming Yu presented on his new and upcoming research that focused on the role of TMPRSS1 and the expression of hepsin in the development of the tectorial membrane (TM), a vital anatomic feature of the auditory system. Deaf mice with notable TM morphogenesis were injected with strains of wild-type human hepsin and a serine protease-dead mutant of human hepsin. The structure of the TM in mice injected with human hepsin were found to have greater structural integrity and increase the quality of auditory function. On the other hand, the serine protease-dead mutant did not produce any hepsin, ultimately resulting in no improvements in the function of the mice. Though this research is still in the manuscript stage of development, it begs the question: how can this research advance medical research to help humans with genetic deafness?

    Previous research conducted in 2018 by Dr. Hena Ahmed explores this possibility in the realm of gene therapy in relation to deficiencies in the TMPRSS3 protein. Similar to the role of TMPRSS1 in the development of the tectorial membrane, TMPRSS3 influences the development of the hair cells and organ of Corti found in the signaling pathway of the auditory systems. The control of the experiment included deaf wild-type mice with sparse amounts of hair cells and the experimental group included mice injected in vivo with TMPRSS3 gene therapy. The results showed that the experimental group with higher expression of TMPRSS3 improved in their hearing functional tests as well as developed an increased density of hair cells in the inner ear, indicating a positive relationship between them. In the end of her abstract, Dr. Ahmed expresses that this research can serve as a gateway in advancing gene therapies to aid those with hereditary deafness. It would be worth exploring the specific functions of each of the varying proteases in the TMPRSS family and their relationship to the morphology of different anatomical auditory structures that influence the different causes of inhibited auditory function. 

References:

Ahmed, H. (2018). Tmprss3 gene expression and gene therapy in a mouse model of human deafness (Order No. 28266463). Available from ProQuest Dissertations & Theses Global. (2486561163). Retrieved from https://flagship.luc.edu/login?url=https://www.proquest.com/dissertations-theses/em-tmprss3-gene-expression-therapy-mouse-model/docview/2486561163/se-2

Yu, W.M. (2024). Critical role of hepsin/TMPRSS1 in hearing and tectorial membrane morphogenesis: insights from transgenic mouse models