Comparison of the fertility of tumor suppressor gene-deficient C57BL/6 mouse strains reveals stable reproductive aging and novel pleiotropic gene

Abstract Tumor suppressor genes are involved in maintaining genome integrity during reproduction (e.g., meiosis). Thus, deleterious alleles in tumor suppressor-deficient mice would exhibit higher mortality during the perinatal period. A recent aging model proposes that perinatal mortality and age-re...

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Autores principales:	Masaoki Kohzaki, Akira Ootsuyama, Toshiyuki Umata, Ryuji Okazaki
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/ae51f3e286524bcbacde0b1bd96086a3
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spelling	oai:doaj.org-article:ae51f3e286524bcbacde0b1bd96086a32021-12-02T17:52:12ZComparison of the fertility of tumor suppressor gene-deficient C57BL/6 mouse strains reveals stable reproductive aging and novel pleiotropic gene10.1038/s41598-021-91342-92045-2322https://doaj.org/article/ae51f3e286524bcbacde0b1bd96086a32021-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-91342-9https://doaj.org/toc/2045-2322Abstract Tumor suppressor genes are involved in maintaining genome integrity during reproduction (e.g., meiosis). Thus, deleterious alleles in tumor suppressor-deficient mice would exhibit higher mortality during the perinatal period. A recent aging model proposes that perinatal mortality and age-related deleterious changes might define lifespan. This study aimed to quantitatively understand the relationship between reproduction and lifespan using three established tumor suppressor gene (p53, APC, and RECQL4)-deficient mouse strains with the same C57BL/6 background. Transgenic mice delivered slightly reduced numbers of 1st pups than wild-type mice [ratio: 0.81–0.93 (p = 0.1–0.61)] during a similar delivery period, which suggest that the tumor suppressor gene-deficient mice undergo relatively stable reproduction. However, the transgenic 1st pups died within a few days after birth, resulting in a further reduction in litter size at 3 weeks after delivery compared with that of wild-type mice [ratio: 0.35–0.68 (p = 0.034–0.24)] without sex differences, although the lifespan was variable. Unexpectedly, the significance of reproductive reduction in transgenic mice was decreased at the 2nd or later delivery. Because mice are easily affected by environmental factors, our data underscore the importance of defining reproductive ability through experiments on aging-related reproduction that can reveal a trade-off between fecundity and aging and identify RECQL4 as a novel pleiotropic gene.Masaoki KohzakiAkira OotsuyamaToshiyuki UmataRyuji OkazakiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Masaoki Kohzaki Akira Ootsuyama Toshiyuki Umata Ryuji Okazaki Comparison of the fertility of tumor suppressor gene-deficient C57BL/6 mouse strains reveals stable reproductive aging and novel pleiotropic gene
description	Abstract Tumor suppressor genes are involved in maintaining genome integrity during reproduction (e.g., meiosis). Thus, deleterious alleles in tumor suppressor-deficient mice would exhibit higher mortality during the perinatal period. A recent aging model proposes that perinatal mortality and age-related deleterious changes might define lifespan. This study aimed to quantitatively understand the relationship between reproduction and lifespan using three established tumor suppressor gene (p53, APC, and RECQL4)-deficient mouse strains with the same C57BL/6 background. Transgenic mice delivered slightly reduced numbers of 1st pups than wild-type mice [ratio: 0.81–0.93 (p = 0.1–0.61)] during a similar delivery period, which suggest that the tumor suppressor gene-deficient mice undergo relatively stable reproduction. However, the transgenic 1st pups died within a few days after birth, resulting in a further reduction in litter size at 3 weeks after delivery compared with that of wild-type mice [ratio: 0.35–0.68 (p = 0.034–0.24)] without sex differences, although the lifespan was variable. Unexpectedly, the significance of reproductive reduction in transgenic mice was decreased at the 2nd or later delivery. Because mice are easily affected by environmental factors, our data underscore the importance of defining reproductive ability through experiments on aging-related reproduction that can reveal a trade-off between fecundity and aging and identify RECQL4 as a novel pleiotropic gene.
format	article
author	Masaoki Kohzaki Akira Ootsuyama Toshiyuki Umata Ryuji Okazaki
author_facet	Masaoki Kohzaki Akira Ootsuyama Toshiyuki Umata Ryuji Okazaki
author_sort	Masaoki Kohzaki
title	Comparison of the fertility of tumor suppressor gene-deficient C57BL/6 mouse strains reveals stable reproductive aging and novel pleiotropic gene
title_short	Comparison of the fertility of tumor suppressor gene-deficient C57BL/6 mouse strains reveals stable reproductive aging and novel pleiotropic gene
title_full	Comparison of the fertility of tumor suppressor gene-deficient C57BL/6 mouse strains reveals stable reproductive aging and novel pleiotropic gene
title_fullStr	Comparison of the fertility of tumor suppressor gene-deficient C57BL/6 mouse strains reveals stable reproductive aging and novel pleiotropic gene
title_full_unstemmed	Comparison of the fertility of tumor suppressor gene-deficient C57BL/6 mouse strains reveals stable reproductive aging and novel pleiotropic gene
title_sort	comparison of the fertility of tumor suppressor gene-deficient c57bl/6 mouse strains reveals stable reproductive aging and novel pleiotropic gene
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/ae51f3e286524bcbacde0b1bd96086a3
work_keys_str_mv	AT masaokikohzaki comparisonofthefertilityoftumorsuppressorgenedeficientc57bl6mousestrainsrevealsstablereproductiveagingandnovelpleiotropicgene AT akiraootsuyama comparisonofthefertilityoftumorsuppressorgenedeficientc57bl6mousestrainsrevealsstablereproductiveagingandnovelpleiotropicgene AT toshiyukiumata comparisonofthefertilityoftumorsuppressorgenedeficientc57bl6mousestrainsrevealsstablereproductiveagingandnovelpleiotropicgene AT ryujiokazaki comparisonofthefertilityoftumorsuppressorgenedeficientc57bl6mousestrainsrevealsstablereproductiveagingandnovelpleiotropicgene
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Comparison of the fertility of tumor suppressor gene-deficient C57BL/6 mouse strains reveals stable reproductive aging and novel pleiotropic gene

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