Urine-based Detection of Congenital Portosystemic Shunt in C57BL/6 Mice

Abstract Sporadic occurrence of congenital portosystemic shunt (PSS) at a rate ∼1 out 10 among C57BL/6 mice, which are widely used in biomedical research, results aberrancies serologic, metabolic, and physiologic parameters. Therefore, mice with PSS should be identified as outliers research. Accordingly, we sought methods to, reliably efficiently, identify mice. Serum total bile acids ≥ 40 µM is bona fide biomarker but utility this limited by its cost invasiveness, particularly if large numbers to screened. This led us investigate assay urine might serve simple, inexpensive, non-invasive means diagnosis. Metabolome profiling uncovered that Krebs cycle intermediates, i.e., citrate, α-ketoglutarate, fumarate, were strikingly distinctly elevated the We leveraged iron-chelating pH-lowering properties such metabolites basis for three urine-based screening tests: urinary iron-chelation assay, pH strip test, phenol red assay. Our findings demonstrate feasibility using these colorimetric assays, whereby their readout can assessed direct observation, diagnose an rapid, manner. Application our protocols aid research enabling stratification which, present, likely confound numerous ongoing studies.