Improved Growth Patterns in Cystic Fibrosis Mice after Loss of Histone Deacetylase 6

Abstract Growth failure in cystic fibrosis (CF) patients has been well-documented and shown to correlate with poorer disease outcomes. This observation is also true in CF animal models, including mouse, pig, rat, and ferret. The etiology underlying growth deficits is unknown, and our previous work d...

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Autores principales:	Sharon M. Rymut, Deborah A. Corey, Dana M. Valerio, Bernadette O. Erokwu, Chris A. Flask, Thomas J. Kelley, Craig A. Hodges
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/fe1f349f88014e678cceaef9c8ae403c
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spelling	oai:doaj.org-article:fe1f349f88014e678cceaef9c8ae403c2021-12-02T12:32:51ZImproved Growth Patterns in Cystic Fibrosis Mice after Loss of Histone Deacetylase 610.1038/s41598-017-03931-22045-2322https://doaj.org/article/fe1f349f88014e678cceaef9c8ae403c2017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-03931-2https://doaj.org/toc/2045-2322Abstract Growth failure in cystic fibrosis (CF) patients has been well-documented and shown to correlate with poorer disease outcomes. This observation is also true in CF animal models, including mouse, pig, rat, and ferret. The etiology underlying growth deficits is unknown, and our previous work demonstrated reduced tubulin acetylation in CF cell models and tissue that is correctable by inhibition of histone deacetylase-6 (HDAC6). Here, we hypothesize that loss of HDAC6 will improve growth phenotype in a CF mouse model. Hdac6 knockout mice were crossed with F508del (CF) mice to generate F508del/Hdac6 (CF/HDA) mice. Growth, fat deposits, survival, and bioelectric measurements were analyzed. CF/HDA mice displayed improvements in length and weight with no correction of CFTR function. Mechanistically, Igf1 levels likely account for increased length and improvements in fertility. Weight gain is attributed to increased fat deposits potentially mediated by increased adipocyte differentiation. CF-related growth deficits can be improved via inhibition of HDAC6, further implicating it as a potential therapeutic target for CF.Sharon M. RymutDeborah A. CoreyDana M. ValerioBernadette O. ErokwuChris A. FlaskThomas J. KelleyCraig A. HodgesNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-11 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Sharon M. Rymut Deborah A. Corey Dana M. Valerio Bernadette O. Erokwu Chris A. Flask Thomas J. Kelley Craig A. Hodges Improved Growth Patterns in Cystic Fibrosis Mice after Loss of Histone Deacetylase 6
description	Abstract Growth failure in cystic fibrosis (CF) patients has been well-documented and shown to correlate with poorer disease outcomes. This observation is also true in CF animal models, including mouse, pig, rat, and ferret. The etiology underlying growth deficits is unknown, and our previous work demonstrated reduced tubulin acetylation in CF cell models and tissue that is correctable by inhibition of histone deacetylase-6 (HDAC6). Here, we hypothesize that loss of HDAC6 will improve growth phenotype in a CF mouse model. Hdac6 knockout mice were crossed with F508del (CF) mice to generate F508del/Hdac6 (CF/HDA) mice. Growth, fat deposits, survival, and bioelectric measurements were analyzed. CF/HDA mice displayed improvements in length and weight with no correction of CFTR function. Mechanistically, Igf1 levels likely account for increased length and improvements in fertility. Weight gain is attributed to increased fat deposits potentially mediated by increased adipocyte differentiation. CF-related growth deficits can be improved via inhibition of HDAC6, further implicating it as a potential therapeutic target for CF.
format	article
author	Sharon M. Rymut Deborah A. Corey Dana M. Valerio Bernadette O. Erokwu Chris A. Flask Thomas J. Kelley Craig A. Hodges
author_facet	Sharon M. Rymut Deborah A. Corey Dana M. Valerio Bernadette O. Erokwu Chris A. Flask Thomas J. Kelley Craig A. Hodges
author_sort	Sharon M. Rymut
title	Improved Growth Patterns in Cystic Fibrosis Mice after Loss of Histone Deacetylase 6
title_short	Improved Growth Patterns in Cystic Fibrosis Mice after Loss of Histone Deacetylase 6
title_full	Improved Growth Patterns in Cystic Fibrosis Mice after Loss of Histone Deacetylase 6
title_fullStr	Improved Growth Patterns in Cystic Fibrosis Mice after Loss of Histone Deacetylase 6
title_full_unstemmed	Improved Growth Patterns in Cystic Fibrosis Mice after Loss of Histone Deacetylase 6
title_sort	improved growth patterns in cystic fibrosis mice after loss of histone deacetylase 6
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/fe1f349f88014e678cceaef9c8ae403c
work_keys_str_mv	AT sharonmrymut improvedgrowthpatternsincysticfibrosismiceafterlossofhistonedeacetylase6 AT deborahacorey improvedgrowthpatternsincysticfibrosismiceafterlossofhistonedeacetylase6 AT danamvalerio improvedgrowthpatternsincysticfibrosismiceafterlossofhistonedeacetylase6 AT bernadetteoerokwu improvedgrowthpatternsincysticfibrosismiceafterlossofhistonedeacetylase6 AT chrisaflask improvedgrowthpatternsincysticfibrosismiceafterlossofhistonedeacetylase6 AT thomasjkelley improvedgrowthpatternsincysticfibrosismiceafterlossofhistonedeacetylase6 AT craigahodges improvedgrowthpatternsincysticfibrosismiceafterlossofhistonedeacetylase6
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Improved Growth Patterns in Cystic Fibrosis Mice after Loss of Histone Deacetylase 6

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