title: ¹H NMR metabolic profiling of plasma reveals additional phenotypes in knockout mouse models.
abstract: 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 ((1)H NMR) spectroscopy. (1)H 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 (1)H NMR glucose measurement was 12%, and the (1)H NMR spectroscopy data were influenced by gender and feeding status. There were good correlations between the clinical chemistry and the (1)H 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 (1)H NMR spectroscopy, clinical chemistry, and histopathology. In a further two KO lines, Elmod1 (MGI: 3583900) and Emc10 (MGI: 1916933), (1)H 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 (1)H NMR spectroscopy can therefore provide a novel perspective on the function of knocked-out genes.
authors: †Mary Lyon Centre, MRC Harwell, Oxfordshire OX11 0RD, United Kingdom.|‡Institute of Hepatology, Foundation for Liver Research, 69-75 Chenies Mews, London WC1E 6HX, United Kingdom.
authors: Fay
authors: F
authors: Probert
authors: †Mary Lyon Centre, MRC Harwell, Oxfordshire OX11 0RD, United Kingdom.
authors: Paul
authors: P
authors: Rice
authors: †Mary Lyon Centre, MRC Harwell, Oxfordshire OX11 0RD, United Kingdom.
authors: Cheryl L
authors: CL
authors: Scudamore
authors: †Mary Lyon Centre, MRC Harwell, Oxfordshire OX11 0RD, United Kingdom.
authors: Sara
authors: S
authors: Wells
authors: ‡Institute of Hepatology, Foundation for Liver Research, 69-75 Chenies Mews, London WC1E 6HX, United Kingdom.
authors: Roger
authors: R
authors: Williams
authors: †Mary Lyon Centre, MRC Harwell, Oxfordshire OX11 0RD, United Kingdom.
authors: Tertius A
authors: TA
authors: Hough
authors: ‡Institute of Hepatology, Foundation for Liver Research, 69-75 Chenies Mews, London WC1E 6HX, United Kingdom.
authors: I Jane
authors: IJ
authors: Cox
mesh_terms: D000818:Animals; D001842:Bone and Bones / Q000737:chemistry / Q000378:metabolism; D005260:Female; D006579:Heterozygote; D006720:Homozygote; D007668:Kidney / Q000737:chemistry / Q000378:metabolism; D008099:Liver / Q000737:chemistry / Q000378:metabolism; D008297:Male; D055442:Metabolome; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout / Q000097:blood* / Q000235:genetics; D010641:Phenotype; D025341:Principal Component Analysis; D066244:Proton Magnetic Resonance Spectroscopy
keywords: knockout mouse; liver; metabolomics; metabonomics; phenotyping screen; plasma; proton nuclear magnetic resonance spectroscopy