PMID- 30788385
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20200929
IS  - 2329-0501 (Print)
IS  - 2329-0501 (Electronic)
IS  - 2329-0501 (Linking)
VI  - 13
DP  - 2019 Jun 14
TI  - AAV9-TAZ Gene Replacement Ameliorates Cardiac TMT Proteomic Profiles in a Mouse 
      Model of Barth Syndrome.
PG  - 167-179
LID - 10.1016/j.omtm.2019.01.007 [doi]
AB  - Barth syndrome (BTHS) is a rare mitochondrial disease that causes severe 
      cardiomyopathy and has no disease-modifying therapy. It is caused by recessive 
      mutations in the gene tafazzin (TAZ), which encodes tafazzin-an acyltransferase 
      that remodels the inner mitochondrial membrane lipid cardiolipin. To identify 
      novel mechanistic pathways involved in BTHS and evaluate the effects of gene 
      therapy on proteomic profiles, we performed a multiplex tandem mass tagging (TMT) 
      quantitative proteomics analysis to compare protein expression profiles from 
      heart lysates isolated from BTHS, healthy wild-type (WT), and BTHS treated with 
      adeno-associated virus serotype 9 (AAV9)-TAZ gene replacement as neonates or 
      adults. 197 proteins with >/=2 unique peptides were identified. Of these, 91 
      proteins were significantly differentially expressed in BTHS compared to WT 
      controls. Cause-effect relationships between tafazzin deficiency and altered 
      protein profiles were confirmed through demonstrated significant improvements in 
      expression levels following administration of AAV9-TAZ. The importance of TMEM65 
      in Cx43 localization to cardiac intercalated discs was revealed as a novel 
      consequence of tafazzin deficiency that was improved following gene therapy. This 
      study identifies novel mechanistic pathways involved in the pathophysiology of 
      BTHS, demonstrates the ability of gene delivery to improve protein expression 
      profiles, and provides support for clinical translation of AAV9-TAZ gene therapy.
FAU - Suzuki-Hatano, Silveli
AU  - Suzuki-Hatano S
AD  - Department of Pediatrics, University of Florida College of Medicine, Gainesville, 
      FL 32610, USA.
FAU - Saha, Madhurima
AU  - Saha M
AD  - Department of Pediatrics, University of Florida College of Medicine, Gainesville, 
      FL 32610, USA.
FAU - Soustek, Meghan S
AU  - Soustek MS
AD  - Department of Pediatrics, University of Florida College of Medicine, Gainesville, 
      FL 32610, USA.
AD  - Department of Molecular Genetics and Microbiology, University of Florida College 
      of Medicine, Gainesville, FL 32610, USA.
FAU - Kang, Peter B
AU  - Kang PB
AD  - Department of Pediatrics, University of Florida College of Medicine, Gainesville, 
      FL 32610, USA.
AD  - Department of Molecular Genetics and Microbiology, University of Florida College 
      of Medicine, Gainesville, FL 32610, USA.
FAU - Byrne, Barry J
AU  - Byrne BJ
AD  - Department of Pediatrics, University of Florida College of Medicine, Gainesville, 
      FL 32610, USA.
AD  - Department of Molecular Genetics and Microbiology, University of Florida College 
      of Medicine, Gainesville, FL 32610, USA.
FAU - Cade, W Todd
AU  - Cade WT
AD  - Program in Physical Therapy, Washington University School of Medicine, St. Louis, 
      MO 63110, USA.
FAU - Pacak, Christina A
AU  - Pacak CA
AD  - Department of Pediatrics, University of Florida College of Medicine, Gainesville, 
      FL 32610, USA.
AD  - Department of Molecular Genetics and Microbiology, University of Florida College 
      of Medicine, Gainesville, FL 32610, USA.
LA  - eng
GR  - R01 HL107406/HL/NHLBI NIH HHS/United States
GR  - R01 HL136759/HL/NHLBI NIH HHS/United States
PT  - Journal Article
DEP - 20190125
PL  - United States
TA  - Mol Ther Methods Clin Dev
JT  - Molecular therapy. Methods & clinical development
JID - 101624857
PMC - PMC6369239
OTO - NOTNLM
OT  - AAV9
OT  - BTHS
OT  - Barth syndrome
OT  - Cx43
OT  - TMEM65
OT  - TMT proteomics
OT  - cardiac gene therapy
OT  - gap junction localization
OT  - mitochondrial disease
OT  - tafazzin
EDAT- 2019/02/23 06:00
MHDA- 2019/02/23 06:01
PMCR- 2019/01/25
CRDT- 2019/02/22 06:00
PHST- 2018/08/24 00:00 [received]
PHST- 2019/01/16 00:00 [accepted]
PHST- 2019/02/22 06:00 [entrez]
PHST- 2019/02/23 06:00 [pubmed]
PHST- 2019/02/23 06:01 [medline]
PHST- 2019/01/25 00:00 [pmc-release]
AID - S2329-0501(19)30010-5 [pii]
AID - 10.1016/j.omtm.2019.01.007 [doi]
PST - epublish
SO  - Mol Ther Methods Clin Dev. 2019 Jan 25;13:167-179. doi: 
      10.1016/j.omtm.2019.01.007. eCollection 2019 Jun 14.