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Inferring Somatic Mutation Rates Using the Stop-Enhanced Green Fluorescent Protein Mouse

Authors
 Simon Ro  ;  Bruce Rannala 
Citation
 GENETICS, Vol.177(1) : 9-16, 2007 
Journal Title
 GENETICS 
ISSN
 0016-6731 
Issue Date
2007
MeSH
Animals ; Codon, Terminator* ; Ethylnitrosourea/toxicity ; Green Fluorescent Proteins/genetics* ; Green Fluorescent Proteins/metabolism* ; Liver/pathology ; Mice ; Models, Biological ; Mutagenicity Tests ; Mutagens/toxicity ; Mutation/genetics* ; Stem Cells/cytology ; Stem Cells/physiology*
Abstract
A new method is developed for estimating rates of somatic mutation in vivo. The stop-enhanced green fluorescent protein (EGFP) transgenic mouse carries multiple copies of an EGFP gene with a premature stop codon. The gene can revert to a functional form via point mutations. Mice treated with a potent mutagen, N-ethyl-N-nitrosourea (ENU), and mice treated with a vehicle alone are assayed for mutations in liver cells. A stochastic model is developed to model the mutation and gene expression processes and maximum-likelihood estimators of the model parameters are derived. A likelihood-ratio test (LRT) is developed for detecting mutagenicity. Parametric bootstrap simulations are used to obtain confidence intervals of the parameter estimates and to estimate the significance of the LRT. The LRT is highly significant (alpha < 0.01) and the 95% confidence interval for the relative effect of the mutagen (the ratio of the rate of mutation during the interval of mutagen exposure to the rate of background mutation) ranges from a minimum 200-fold effect of the mutagen to a maximum 2000-fold effect.
Files in This Item:
T200705177.pdf Download
DOI
10.1534/genetics.106.069310
Appears in Collections:
5. Research Institutes (연구소) > Liver Cirrhosis Clinical Research Center (간경변증임상연구센터) > 1. Journal Papers
Yonsei Authors
Ro, Simon Weonsang(노원상) ORCID logo https://orcid.org/0000-0003-2187-3698
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/96051
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