Lukas Lohmeyer
Pronouns: He/him
Research Mentor(s): Yusheng Liang
Research Mentor School/College/Department: MIP / Medicine
Program: UROP
Session: Session 7 (4:40pm – 5:30pm)
Authors: Lukas Lohmeyer, Yusheng Liang , Lukas Lohmeyer
Abstract
For growth, skeletal muscle requires a healthy balance between protein synthesis and degradation. The endoplasmic reticulum (ER) is the primary locus of protein folding and synthesis in mammalian cells. Failure to degrade misfolded proteins that accumulate in the ER results in the loss of ER homeostasis which can generate a plethora of health issues. ER associated degradation (ERAD) is one mechanism responsible for targeting misfolded ER proteins for cytosolic degradation. The exact mechanistic pathway in which this is done, however, remains unclear. Here, we look into the role of the SEl1L-HRD1 ERAD complex, the most highly conserved subunit of ERAD in skeletal muscle, using the Sel1L muscle specific knockout mouse model. This study utilizes Wild Type (WT) and Sel1L Knockout mice (SKO). Flox Flox and Cre mice are crossed to produce SKO mice. Genotyping for mice is performed with ear tissue using DNA extraction and DNA gel electrophoresis to identify Cre and Flox Flox markers, allowing for identification of SKO mice. WT and SKO mice are routinely weighed. Muscle mass is collected via dissection and weighed. Histology is utilized in conjunction with ImageJ software to quantify average cross sectional area of muscle fibers. Current results show that SKO and WT body weight diverges around 5 weeks as, at this point, SKO growth stagnates. Results also show SKO mice experience progressive muscle wasting and kyphosis with age which suggests they are likely to experience dystrophy. While current findings are useful, further work is needed to fully answer our research question. We will continue to work to acquire evidence that SKO mice do experience muscle dystrophy and to identify the exact substrates and mechanisms responsible for the SKO phenotype. This work will provide an understanding of which loci to target when treating ER dyshomeostasis associated disease.
