1H NMR Metabolic Profiling of Plasma Reveals Additional Phenotypes in Knockout Mouse Models

The International Mouse Phenotyping Consortium program has been established to ascribe biological functions to systematically knocked-out (KO) genes by in vivo and ex vivo phenotyping. The plasma clinical chemistry screen includes an assessment of liver, kidney, and bone function and provides a basic lipid profile and histopathology reports on 32 tissues. We report on the inclusion of plasma analysis by proton nuclear magnetic resonance (H-1 NMR) spectroscopy. H-1 NMR spectroscopy data are summarized from 116 running baseline controls with 18 homozygous and 2 heterozygous KO mouse lines along with wild-type controls (typically n = 7 per gender). For the baseline group, the intersample variation of H-1 NMR glucose measurement was 12%, and the H-1 NMR spectroscopy data were influenced by gender and feeding status. There were good correlations between the clinical chemistry and the H-1 NMR spectroscopy measurements for glucose, triglycerides, and HDL cholesterol. Significant differences were observed in two KO lines, Agl (MGI: 1924809) and Bbs5 (MGI: 1919819), by H-1 NMR spectroscopy, clinical chemistry, and histopathology. In a further two KO lines, Elmod1 (MGI: 3583900) and Emc10 (MGI: 1916933), H-1 NMR metabolic differences were observed, but no other ex vivo changes were detected. In the remaining 16 lines, no ex vivo abnormal phenotypes were observed. Plasma H-1 NMR spectroscopy can therefore provide a novel perspective on the function of knocked-out genes.