Sexually dimorphic leanness and hypermobility in p16 Ink4a /CDKN2A-deficient mice coincides with phenotypic changes in the cerebellum

Abstract p16 Ink4a /CDKN2A is a tumor suppressor that critically regulates the cell cycle. Indeed, p16 Ink4a deficiency promotes tumor formation in various tissues. We now report that p16 Ink4a deficiency in female mice, but not male mice, induces leanness especially in old age, as indicated by lowe...

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Autores principales:	Kwang H. Kim, Yejin Cho, Jaehoon Lee, Haengdueng Jeong, Yura Lee, Soo In Kim, Chang-Hoon Kim, Han-Woong Lee, Ki Taek Nam
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2019
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/323f75e31e8349f98e967ae959e242b5
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spelling	oai:doaj.org-article:323f75e31e8349f98e967ae959e242b52021-12-02T15:08:09ZSexually dimorphic leanness and hypermobility in p16 Ink4a /CDKN2A-deficient mice coincides with phenotypic changes in the cerebellum10.1038/s41598-019-47676-62045-2322https://doaj.org/article/323f75e31e8349f98e967ae959e242b52019-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-019-47676-6https://doaj.org/toc/2045-2322Abstract p16 Ink4a /CDKN2A is a tumor suppressor that critically regulates the cell cycle. Indeed, p16 Ink4a deficiency promotes tumor formation in various tissues. We now report that p16 Ink4a deficiency in female mice, but not male mice, induces leanness especially in old age, as indicated by lower body weight and smaller white adipose tissue, although other major organs are unaffected. Unexpectedly, the integrity, number, and sizes of adipocytes in white adipose tissue were unaffected, as was macrophage infiltration. Hence, hypermobility appeared to be accountable for the phenotype, since food consumption was not altered. Histological analysis of the cerebellum and deep cerebellar nuclei, a vital sensorimotor control center, revealed increased proliferation of neuronal cells and improved cerebellum integrity. Expression of estrogen receptor β (ERβ) and PCNA also increased in deep cerebellar nuclei, implying crosstalk between p16 Ink4a and ERβ. Furthermore, p16 Ink4a deficiency expands LC3B+ cells and GFAP+ astrocytes in response to estrogen. Collectively, the data suggest that loss of p16 INK4a induces sexually dimorphic leanness in female mice, which appears to be due to protection against cerebellar senescence by promoting neuronal proliferation and homeostasis via ERβ.Kwang H. KimYejin ChoJaehoon LeeHaengdueng JeongYura LeeSoo In KimChang-Hoon KimHan-Woong LeeKi Taek NamNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 9, Iss 1, Pp 1-10 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Kwang H. Kim Yejin Cho Jaehoon Lee Haengdueng Jeong Yura Lee Soo In Kim Chang-Hoon Kim Han-Woong Lee Ki Taek Nam Sexually dimorphic leanness and hypermobility in p16 Ink4a /CDKN2A-deficient mice coincides with phenotypic changes in the cerebellum
description	Abstract p16 Ink4a /CDKN2A is a tumor suppressor that critically regulates the cell cycle. Indeed, p16 Ink4a deficiency promotes tumor formation in various tissues. We now report that p16 Ink4a deficiency in female mice, but not male mice, induces leanness especially in old age, as indicated by lower body weight and smaller white adipose tissue, although other major organs are unaffected. Unexpectedly, the integrity, number, and sizes of adipocytes in white adipose tissue were unaffected, as was macrophage infiltration. Hence, hypermobility appeared to be accountable for the phenotype, since food consumption was not altered. Histological analysis of the cerebellum and deep cerebellar nuclei, a vital sensorimotor control center, revealed increased proliferation of neuronal cells and improved cerebellum integrity. Expression of estrogen receptor β (ERβ) and PCNA also increased in deep cerebellar nuclei, implying crosstalk between p16 Ink4a and ERβ. Furthermore, p16 Ink4a deficiency expands LC3B+ cells and GFAP+ astrocytes in response to estrogen. Collectively, the data suggest that loss of p16 INK4a induces sexually dimorphic leanness in female mice, which appears to be due to protection against cerebellar senescence by promoting neuronal proliferation and homeostasis via ERβ.
format	article
author	Kwang H. Kim Yejin Cho Jaehoon Lee Haengdueng Jeong Yura Lee Soo In Kim Chang-Hoon Kim Han-Woong Lee Ki Taek Nam
author_facet	Kwang H. Kim Yejin Cho Jaehoon Lee Haengdueng Jeong Yura Lee Soo In Kim Chang-Hoon Kim Han-Woong Lee Ki Taek Nam
author_sort	Kwang H. Kim
title	Sexually dimorphic leanness and hypermobility in p16 Ink4a /CDKN2A-deficient mice coincides with phenotypic changes in the cerebellum
title_short	Sexually dimorphic leanness and hypermobility in p16 Ink4a /CDKN2A-deficient mice coincides with phenotypic changes in the cerebellum
title_full	Sexually dimorphic leanness and hypermobility in p16 Ink4a /CDKN2A-deficient mice coincides with phenotypic changes in the cerebellum
title_fullStr	Sexually dimorphic leanness and hypermobility in p16 Ink4a /CDKN2A-deficient mice coincides with phenotypic changes in the cerebellum
title_full_unstemmed	Sexually dimorphic leanness and hypermobility in p16 Ink4a /CDKN2A-deficient mice coincides with phenotypic changes in the cerebellum
title_sort	sexually dimorphic leanness and hypermobility in p16 ink4a /cdkn2a-deficient mice coincides with phenotypic changes in the cerebellum
publisher	Nature Portfolio
publishDate	2019
url	https://doaj.org/article/323f75e31e8349f98e967ae959e242b5
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Sexually dimorphic leanness and hypermobility in p16 Ink4a /CDKN2A-deficient mice coincides with phenotypic changes in the cerebellum

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