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The C57BL/6J Mouse Strain Background Modifies the Effect of a Mutation in Bcl2l2

Bcl2l2 encodes BCL-W, an antiapoptotic member of the BCL-2 family of proteins. Intercross of Bcl2l2 +/− mice on a mixed C57BL/6J, 129S5 background produces Bcl2l2 −/− animals with the expected frequency. In contrast, intercross of Bcl2l2 +/− mice on a congenic C57BL/6J background produces relatively...

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Autores principales: Navarro, Stefanie J., Trinh, Tuyen, Lucas, Charlotte A., Ross, Andrea J., Waymire, Katrina G., MacGregor, Grant R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Genetics Society of America 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3276190/
https://www.ncbi.nlm.nih.gov/pubmed/22384386
http://dx.doi.org/10.1534/g3.111.000778
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author Navarro, Stefanie J.
Trinh, Tuyen
Lucas, Charlotte A.
Ross, Andrea J.
Waymire, Katrina G.
MacGregor, Grant R.
author_facet Navarro, Stefanie J.
Trinh, Tuyen
Lucas, Charlotte A.
Ross, Andrea J.
Waymire, Katrina G.
MacGregor, Grant R.
author_sort Navarro, Stefanie J.
collection PubMed
description Bcl2l2 encodes BCL-W, an antiapoptotic member of the BCL-2 family of proteins. Intercross of Bcl2l2 +/− mice on a mixed C57BL/6J, 129S5 background produces Bcl2l2 −/− animals with the expected frequency. In contrast, intercross of Bcl2l2 +/− mice on a congenic C57BL/6J background produces relatively few live-born Bcl2l2 −/− animals. Genetic modifiers alter the effect of a mutation. C57BL/6J mice (Mus musculus) have a mutant allele of nicotinamide nucleotide transhydrogenase (Nnt) that can act as a modifier. Loss of NNT decreases the concentration of reduced nicotinamide adenine dinucleotide phosphate within the mitochondrial matrix. Nicotinamide adenine dinucleotide phosphate is a cofactor for glutathione reductase, which regenerates reduced glutathione, an important antioxidant. Thus, loss of NNT activity is associated with increased mitochondrial oxidative damage and cellular stress. To determine whether loss of Bcl2l2 −/− mice on the C57BL/6J background was mediated by the Nnt mutation, we outcrossed Bcl2l2 congenic C57BL/6J (Nnt −/−) mice with the closely related C57BL/6JEiJ (Nnt +/+) strain to produce Bcl2l2 +/− ; Nnt +/+ and Bcl2l2 +/− ; Nnt −/− animals. Intercross of Bcl2l2 +/− ; Nnt +/+ mice produced Bcl2l2 −/− with the expected frequency, whereas intercross of Bcl2l2 +/− ; Nnt −/− animals did not. This finding indicates the C57BL/6J strain background, and possibly the Nnt mutation, modifies the Bcl2l2 mutant phenotype. This and previous reports highlight the importance of knowing the genetic composition of mouse strains used in research studies as well as the accurate reporting of mouse strains in the scientific literature.
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spelling pubmed-32761902012-03-01 The C57BL/6J Mouse Strain Background Modifies the Effect of a Mutation in Bcl2l2 Navarro, Stefanie J. Trinh, Tuyen Lucas, Charlotte A. Ross, Andrea J. Waymire, Katrina G. MacGregor, Grant R. G3 (Bethesda) Investigation Bcl2l2 encodes BCL-W, an antiapoptotic member of the BCL-2 family of proteins. Intercross of Bcl2l2 +/− mice on a mixed C57BL/6J, 129S5 background produces Bcl2l2 −/− animals with the expected frequency. In contrast, intercross of Bcl2l2 +/− mice on a congenic C57BL/6J background produces relatively few live-born Bcl2l2 −/− animals. Genetic modifiers alter the effect of a mutation. C57BL/6J mice (Mus musculus) have a mutant allele of nicotinamide nucleotide transhydrogenase (Nnt) that can act as a modifier. Loss of NNT decreases the concentration of reduced nicotinamide adenine dinucleotide phosphate within the mitochondrial matrix. Nicotinamide adenine dinucleotide phosphate is a cofactor for glutathione reductase, which regenerates reduced glutathione, an important antioxidant. Thus, loss of NNT activity is associated with increased mitochondrial oxidative damage and cellular stress. To determine whether loss of Bcl2l2 −/− mice on the C57BL/6J background was mediated by the Nnt mutation, we outcrossed Bcl2l2 congenic C57BL/6J (Nnt −/−) mice with the closely related C57BL/6JEiJ (Nnt +/+) strain to produce Bcl2l2 +/− ; Nnt +/+ and Bcl2l2 +/− ; Nnt −/− animals. Intercross of Bcl2l2 +/− ; Nnt +/+ mice produced Bcl2l2 −/− with the expected frequency, whereas intercross of Bcl2l2 +/− ; Nnt −/− animals did not. This finding indicates the C57BL/6J strain background, and possibly the Nnt mutation, modifies the Bcl2l2 mutant phenotype. This and previous reports highlight the importance of knowing the genetic composition of mouse strains used in research studies as well as the accurate reporting of mouse strains in the scientific literature. Genetics Society of America 2012-01-01 /pmc/articles/PMC3276190/ /pubmed/22384386 http://dx.doi.org/10.1534/g3.111.000778 Text en Copyright © 2012 Navarro et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution Unported License (http://creativecommons.org/licenses/by/3.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Investigation
Navarro, Stefanie J.
Trinh, Tuyen
Lucas, Charlotte A.
Ross, Andrea J.
Waymire, Katrina G.
MacGregor, Grant R.
The C57BL/6J Mouse Strain Background Modifies the Effect of a Mutation in Bcl2l2
title The C57BL/6J Mouse Strain Background Modifies the Effect of a Mutation in Bcl2l2
title_full The C57BL/6J Mouse Strain Background Modifies the Effect of a Mutation in Bcl2l2
title_fullStr The C57BL/6J Mouse Strain Background Modifies the Effect of a Mutation in Bcl2l2
title_full_unstemmed The C57BL/6J Mouse Strain Background Modifies the Effect of a Mutation in Bcl2l2
title_short The C57BL/6J Mouse Strain Background Modifies the Effect of a Mutation in Bcl2l2
title_sort c57bl/6j mouse strain background modifies the effect of a mutation in bcl2l2
topic Investigation
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3276190/
https://www.ncbi.nlm.nih.gov/pubmed/22384386
http://dx.doi.org/10.1534/g3.111.000778
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