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Improved Growth Patterns in Cystic Fibrosis Mice after Loss of Histone Deacetylase 6.
Rymut, Sharon M; Corey, Deborah A; Valerio, Dana M; Erokwu, Bernadette O; Flask, Chris A; Kelley, Thomas J; Hodges, Craig A.
Affiliation
  • Rymut SM; Department of Pediatrics, Case Western Reserve University, Cleveland, Ohio, USA.
  • Corey DA; Department of Pediatrics, Case Western Reserve University, Cleveland, Ohio, USA.
  • Valerio DM; Department of Pediatrics, Case Western Reserve University, Cleveland, Ohio, USA.
  • Erokwu BO; Department of Radiology, Case Western Reserve University, Cleveland, OH, USA.
  • Flask CA; Department of Pediatrics, Case Western Reserve University, Cleveland, Ohio, USA.
  • Kelley TJ; Department of Radiology, Case Western Reserve University, Cleveland, OH, USA.
  • Hodges CA; Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH, USA.
Sci Rep ; 7(1): 3676, 2017 06 16.
Article in En | MEDLINE | ID: mdl-28623308
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.
Subject(s)

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Genetic Predisposition to Disease / Cystic Fibrosis / Histone Deacetylase 6 / Growth Disorders Type of study: Etiology_studies / Prognostic_studies Limits: Animals Language: En Journal: Sci Rep Year: 2017 Document type: Article Affiliation country:

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Genetic Predisposition to Disease / Cystic Fibrosis / Histone Deacetylase 6 / Growth Disorders Type of study: Etiology_studies / Prognostic_studies Limits: Animals Language: En Journal: Sci Rep Year: 2017 Document type: Article Affiliation country: