huMYOC Mouse

The MYOC gene encodes a secreted glycoprotein known as myocilin, which is characterized by an N-terminal leucine zipper motif and a C-terminal olfactomedin-like domain ^[1]. Although myocilin is expressed in various tissues throughout the body—including skeletal muscle, heart, and the lining of the eye—it is most critically labeled and studied in the trabecular meshwork (TM) of the eye, where it is thought to play a role in cytoskeletal organization and cell-matrix interactions ^[2]. While the precise physiological function of myocilin remains a subject of ongoing research, mutations in the MYOC gene are the most common genetic cause of Primary Open-Angle Glaucoma (POAG) and Juvenile Open-Angle Glaucoma (JOAG). In these disease states, misfolded myocilin proteins fail to be secreted and instead accumulate within the endoplasmic reticulum of TM cells, leading to cellular stress, TM dysfunction, and a subsequent increase in intraocular pressure that can damage the optic nerve ^[3].

The huMYOC mouse is a humanized model constructed through gene-editing technology, in which the region from upstream to downstream of the mouse Myoc gene was replaced with the region from upstream to downstream of the human MYOC gene. This model can be used for research on glaucoma, as well as for screening, development, and preclinical evaluation of MYOC-targeted therapeutics.