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Nested retrotransposition in the East Asian mouse genome causes the classical nonagouti mutation

Black coat color (nonagouti) is a widespread classical mutation in laboratory mouse strains. The intronic insertion of endogenous retrovirus VL30 in the nonagouti (a) allele of agouti gene was previously reported as the cause of the nonagouti phenotype. Here, we report agouti mouse strains from East...

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Autores principales: Tanave, Akira, Imai, Yuji, Koide, Tsuyoshi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6677723/
https://www.ncbi.nlm.nih.gov/pubmed/31396563
http://dx.doi.org/10.1038/s42003-019-0539-7
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author Tanave, Akira
Imai, Yuji
Koide, Tsuyoshi
author_facet Tanave, Akira
Imai, Yuji
Koide, Tsuyoshi
author_sort Tanave, Akira
collection PubMed
description Black coat color (nonagouti) is a widespread classical mutation in laboratory mouse strains. The intronic insertion of endogenous retrovirus VL30 in the nonagouti (a) allele of agouti gene was previously reported as the cause of the nonagouti phenotype. Here, we report agouti mouse strains from East Asia that carry the VL30 insertion, indicating that VL30 alone does not cause the nonagouti phenotype. We find that a rare type of endogenous retrovirus, β4, was integrated into the VL30 region at the a allele through nested retrotransposition, causing abnormal splicing. Targeted complete deletion of the β4 element restores agouti gene expression and agouti coat color, whereas deletion of β4 except for a single long terminal repeat results in black-and-tan coat color. Phylogenetic analyses show that the a allele and the β4 retrovirus originated from an East Asian mouse lineage most likely related to Japanese fancy mice. These findings reveal the causal mechanism and historic origin of the classical nonagouti mutation.
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spelling pubmed-66777232019-08-08 Nested retrotransposition in the East Asian mouse genome causes the classical nonagouti mutation Tanave, Akira Imai, Yuji Koide, Tsuyoshi Commun Biol Article Black coat color (nonagouti) is a widespread classical mutation in laboratory mouse strains. The intronic insertion of endogenous retrovirus VL30 in the nonagouti (a) allele of agouti gene was previously reported as the cause of the nonagouti phenotype. Here, we report agouti mouse strains from East Asia that carry the VL30 insertion, indicating that VL30 alone does not cause the nonagouti phenotype. We find that a rare type of endogenous retrovirus, β4, was integrated into the VL30 region at the a allele through nested retrotransposition, causing abnormal splicing. Targeted complete deletion of the β4 element restores agouti gene expression and agouti coat color, whereas deletion of β4 except for a single long terminal repeat results in black-and-tan coat color. Phylogenetic analyses show that the a allele and the β4 retrovirus originated from an East Asian mouse lineage most likely related to Japanese fancy mice. These findings reveal the causal mechanism and historic origin of the classical nonagouti mutation. Nature Publishing Group UK 2019-08-02 /pmc/articles/PMC6677723/ /pubmed/31396563 http://dx.doi.org/10.1038/s42003-019-0539-7 Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Tanave, Akira
Imai, Yuji
Koide, Tsuyoshi
Nested retrotransposition in the East Asian mouse genome causes the classical nonagouti mutation
title Nested retrotransposition in the East Asian mouse genome causes the classical nonagouti mutation
title_full Nested retrotransposition in the East Asian mouse genome causes the classical nonagouti mutation
title_fullStr Nested retrotransposition in the East Asian mouse genome causes the classical nonagouti mutation
title_full_unstemmed Nested retrotransposition in the East Asian mouse genome causes the classical nonagouti mutation
title_short Nested retrotransposition in the East Asian mouse genome causes the classical nonagouti mutation
title_sort nested retrotransposition in the east asian mouse genome causes the classical nonagouti mutation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6677723/
https://www.ncbi.nlm.nih.gov/pubmed/31396563
http://dx.doi.org/10.1038/s42003-019-0539-7
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