A transgenic mouse line for assaying tissue-specific changes in endoplasmic reticulum proteostasis

• DOI: 10.1007/s11248-023-00349-7
• Publication Date: 2023-05-03T09:02:32Z
• Authors: Reinis Svarcbahs; Sarah M. Blossom; Helena S. Baffoe-...; Kathleen A. Trychta; Lacey K. Greer; James Pickel; Mark J. Henderson; Brandon K. Harvey
• Keywords: Proteostasis

Maintenance of calcium homeostasis is important for proper endoplasmic reticulum (ER) function. When cellular stress conditions deplete the high concentration in ER, ER-resident proteins are secreted into extracellular space a process called exodosis. Monitoring exodosis provides insight changes ER and proteostasis resulting from associated with dysregulation. To monitor cell-type specific intact animal, we created transgenic mouse line Gaussia luciferase (GLuc)-based, calcium-modulated protein, SERCaMP, preceded by LoxP-STOP-LoxP (LSL) sequence. The Cre-dependent LSL-SERCaMP mice were crossed albumin (Alb)-Cre dopamine transporter (DAT)-Cre lines. GLuc-SERCaMP expression was characterized organs fluids, secretion response to monitored following pharmacological depletion calcium. In × Alb-Cre mice, robust GLuc activity observed only liver blood, whereas DAT-Cre seen midbrain dopaminergic neurons tissue samples innervated projections. After depletion, saw increased signal plasma cerebrospinal fluid collected crosses, respectively. This model can be used investigate cell types during disease pathogenesis may aid identification therapeutics biomarkers disease.