Journal article
High-throughput screening of mouse knockout lines identifies true lean and obese phenotypes
Obesity (Silver Spring, Md.), Vol.16(10), pp.2362-2367
10/2008
DOI: 10.1038/oby.2008.361
PMID: 18719666
Abstract
We developed a high-throughput approach to knockout (KO) and phenotype mouse orthologs of the 5,000 potential drug targets in the human genome. As part of the phenotypic screen, dual-energy X-ray absorptiometry (DXA) technology estimates body-fat stores in eight KO and four wild-type (WT) littermate chow-fed mice from each line. Normalized % body fat (nBF) (mean KO % body fat/mean WT littermate % body fat) values from the first 2322 lines with viable KO mice at 14 weeks of age showed a normal distribution. We chose to determine how well this screen identifies body-fat phenotypes by selecting 13 of these 2322 KO lines to serve as benchmarks based on their published lean or obese phenotype on a chow diet. The nBF values for the eight benchmark KO lines with a lean phenotype were >= 1 s.d. below the mean for seven (perilipin, SCD1, CB1, MCH1R, PTP1B, GPAT1, PIP5K2B) but close to the mean for NPY Y4R. The nBF values for the five benchmark KO lines with an obese phenotype were >2 s.d. above the mean for four (MC4R, MC3R, BRS3, translin) but close to the mean for 5HT2cR. This screen also identifies novel body-fat phenotypes as exemplified by the obese kinase suppressor of ras 2 (KSR2) KO mice. These body-fat phenotypes were confirmed upon studying additional cohorts of mice for KSR2 and all 13 benchmark KO lines. This simple and cost-effective screen appears capable of identifying genes with a role in regulating mammalian body fat.
Details
- Title: Subtitle
- High-throughput screening of mouse knockout lines identifies true lean and obese phenotypes
- Creators
- Robert Brommage - Lexicon PharmaceuticalsUrvi Desai - Lexicon PharmaceuticalsJean-Pierre Revelli - Lexicon PharmaceuticalsDorit B. Donoviel - Lexicon PharmaceuticalsGregory K. Fontenot - Lexicon PharmaceuticalsChristopher M. DaCosta - Lexicon PharmaceuticalsDeon D. Smith - Lexicon PharmaceuticalsLaura L. Kirkpatrick - Lexicon PharmaceuticalsKenneth J. Coker - Lexicon PharmaceuticalsMichael S. Donoviel - Lexicon PharmaceuticalsDerek E. Eberhart - Lexicon PharmaceuticalsKathleen H. Holt - Lexicon PharmaceuticalsMichael R. Kelly - Lexicon PharmaceuticalsWilliam J. Paradee - Lexicon PharmaceuticalsAnne V. Philips - Lexicon PharmaceuticalsKenneth A. Platt - Lexicon PharmaceuticalsAdisak Suwanichkul - Lexicon PharmaceuticalsGwenn M. Hansen - Lexicon PharmaceuticalsArthur T. Sands - Lexicon PharmaceuticalsBrian P. Zambrowicz - Lexicon PharmaceuticalsDavid R. Powell - Lexicon Pharmaceuticals
- Resource Type
- Journal article
- Publication Details
- Obesity (Silver Spring, Md.), Vol.16(10), pp.2362-2367
- Publisher
- Wiley
- DOI
- 10.1038/oby.2008.361
- PMID
- 18719666
- ISSN
- 1930-7381
- eISSN
- 1930-739X
- Number of pages
- 6
- Language
- English
- Date published
- 10/2008
- Academic Unit
- Medicine Administration
- Record Identifier
- 9984622756902771
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