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.

journal_name

J Proteome Res

authors

Probert F,Rice P,Scudamore CL,Wells S,Williams R,Hough TA,Cox IJ

doi

10.1021/pr501039k

subject

Has Abstract

pub_date

2015-05-01 00:00:00

pages

2036-45

issue

5

eissn

1535-3893

issn

1535-3907

journal_volume

14

pub_type

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