Sgce-KO Mouse

Sgce, also known as ε-Sarcoglycan, is a type Ⅰ single-transmembrane protein. It has been implicated in multiple biological processes. In breast cancer, it is involved in promoting cancer stemness. It interacts with the specific protein 1 transcription factor to increase the transcription of FGF-BP1, activating FGF-FGFR signaling [3]. It also stabilizes EGFR by acting as a sponge molecule for the interaction between EGFR and its E3 ubiquitination ligase, thus promoting breast cancer stem cells [6].

Mutations in Sgce are the most frequent known genetic cause of Myoclonus-Dystonia (M-D), a pleiotropic neuropsychiatric disorder. Patients with SGCE-myoclonus-dystonia often show upper body myoclonus and mild dystonia affecting the neck and arms. Some have gait impairments, like 'circular shaking leg', 'dragging leg', and 'hobby-horse gait' patterns [1,2,7]. SGCE-myoclonus-dystonia may be underdiagnosed due to pleiotropy, mild phenotypes, variable penetrance, and limited access to genetic testing [4]. Loss-of-function mutations in SGCE have been found in Japanese patients with myoclonus-dystonia, with some mutations affecting a brain-specific isoform mostly expressed in the cerebellum, suggesting cerebellar dysfunction as a key element in the pathophysiology [5].

In conclusion, Sgce plays a role in promoting breast cancer stemness through multiple mechanisms. In addition, its mutations are closely associated with Myoclonus-Dystonia, where it shows a variety of motor-related phenotypes. The study of Sgce, especially through understanding its loss-of-function effects, helps in uncovering the pathophysiology of related diseases, providing potential diagnostic and therapeutic targets.