PMID- 27573176
OWN - NLM
STAT- MEDLINE
DCOM- 20171228
LR  - 20240104
IS  - 1748-7838 (Electronic)
IS  - 1001-0602 (Print)
IS  - 1001-0602 (Linking)
VI  - 26
IP  - 10
DP  - 2016 Oct
TI  - Genome editing with CRISPR/Cas9 in postnatal mice corrects PRKAG2 cardiac 
      syndrome.
PG  - 1099-1111
LID - 10.1038/cr.2016.101 [doi]
AB  - PRKAG2 cardiac syndrome is an autosomal dominant inherited disease resulted from 
      mutations in the PRKAG2 gene that encodes gamma2 regulatory subunit of AMP-activated 
      protein kinase. Affected patients usually develop ventricular tachyarrhythmia and 
      experience progressive heart failure that is refractory to medical treatment and 
      requires cardiac transplantation. In this study, we identify a H530R mutation in 
      PRKAG2 from patients with familial Wolff-Parkinson-White syndrome. By generating 
      H530R PRKAG2 transgenic and knock-in mice, we show that both models recapitulate 
      human symptoms including cardiac hypertrophy and glycogen storage, confirming 
      that the H530R mutation is causally related to PRKAG2 cardiac syndrome. We 
      further combine adeno-associated virus-9 (AAV9) and the CRISPR/Cas9 gene-editing 
      system to disrupt the mutant PRKAG2 allele encoding H530R while leaving the 
      wild-type allele intact. A single systemic injection of AAV9-Cas9/sgRNA at 
      postnatal day 4 or day 42 substantially restores the morphology and function of 
      the heart in H530R PRKAG2 transgenic and knock-in mice. Together, our work 
      suggests that in vivo CRISPR/Cas9 genome editing is an effective tool in the 
      treatment of PRKAG2 cardiac syndrome and other dominant inherited cardiac 
      diseases by selectively disrupting disease-causing mutations.
FAU - Xie, Chang
AU  - Xie C
AD  - Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, Wuhan 
      University, Wuhan 430072, China.
AD  - The State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell 
      Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of 
      Sciences, 320 Yue-Yang Road, Shanghai 200031, China.
FAU - Zhang, Ya-Ping
AU  - Zhang YP
AD  - Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan 
      University, Shanghai 200032, China.
FAU - Song, Lu
AU  - Song L
AD  - The State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell 
      Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of 
      Sciences, 320 Yue-Yang Road, Shanghai 200031, China.
FAU - Luo, Jie
AU  - Luo J
AD  - Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, Wuhan 
      University, Wuhan 430072, China.
FAU - Qi, Wei
AU  - Qi W
AD  - The State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell 
      Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of 
      Sciences, 320 Yue-Yang Road, Shanghai 200031, China.
FAU - Hu, Jialu
AU  - Hu J
AD  - Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan 
      University, Shanghai 200032, China.
FAU - Lu, Danbo
AU  - Lu D
AD  - Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan 
      University, Shanghai 200032, China.
FAU - Yang, Zhen
AU  - Yang Z
AD  - Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan 
      University, Shanghai 200032, China.
FAU - Zhang, Jian
AU  - Zhang J
AD  - The State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell 
      Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of 
      Sciences, 320 Yue-Yang Road, Shanghai 200031, China.
FAU - Xiao, Jian
AU  - Xiao J
AD  - Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, Wuhan 
      University, Wuhan 430072, China.
FAU - Zhou, Bin
AU  - Zhou B
AD  - Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, 
      Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 
      Yue-Yang Road, Shanghai 200031, China.
FAU - Du, Jiu-Lin
AU  - Du JL
AD  - Institute of Neuroscience and State Key Laboratory of Neuroscience, Shanghai 
      Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yue-Yang 
      Road, Shanghai 200031, China.
FAU - Jing, Naihe
AU  - Jing N
AD  - The State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell 
      Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of 
      Sciences, 320 Yue-Yang Road, Shanghai 200031, China.
FAU - Liu, Yong
AU  - Liu Y
AD  - Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, Wuhan 
      University, Wuhan 430072, China.
FAU - Wang, Yan
AU  - Wang Y
AD  - Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, Wuhan 
      University, Wuhan 430072, China.
FAU - Li, Bo-Liang
AU  - Li BL
AD  - The State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell 
      Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of 
      Sciences, 320 Yue-Yang Road, Shanghai 200031, China.
FAU - Song, Bao-Liang
AU  - Song BL
AD  - Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, Wuhan 
      University, Wuhan 430072, China.
FAU - Yan, Yan
AU  - Yan Y
AD  - Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan 
      University, Shanghai 200032, China.
LA  - eng
PT  - Journal Article
DEP - 20160830
PL  - England
TA  - Cell Res
JT  - Cell research
JID - 9425763
RN  - 0 (RNA, Guide, CRISPR-Cas Systems)
RN  - EC 2.7.11.1 (PRKAG2 protein, human)
RN  - EC 2.7.11.1 (PRKAG2 protein, mouse)
RN  - EC 2.7.11.31 (AMP-Activated Protein Kinases)
SB  - IM
MH  - AMP-Activated Protein Kinases/deficiency/*genetics/metabolism
MH  - Adenoviridae/genetics
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Alleles
MH  - Animals
MH  - CRISPR-Cas Systems/*genetics
MH  - Child
MH  - Child, Preschool
MH  - Female
MH  - *Gene Editing
MH  - Heart/physiopathology
MH  - Homozygote
MH  - Humans
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Mice, Transgenic
MH  - Middle Aged
MH  - Myocardium/metabolism/pathology
MH  - Polymorphism, Single Nucleotide
MH  - RNA, Guide, CRISPR-Cas Systems/metabolism
MH  - Wolff-Parkinson-White Syndrome/genetics/pathology/*therapy
MH  - Young Adult
PMC - PMC5113300
EDAT- 2016/08/31 06:00
MHDA- 2017/12/29 06:00
PMCR- 2017/10/01
CRDT- 2016/08/31 06:00
PHST- 2016/06/19 00:00 [received]
PHST- 2016/07/10 00:00 [revised]
PHST- 2016/07/11 00:00 [accepted]
PHST- 2016/08/31 06:00 [pubmed]
PHST- 2017/12/29 06:00 [medline]
PHST- 2016/08/31 06:00 [entrez]
PHST- 2017/10/01 00:00 [pmc-release]
AID - cr2016101 [pii]
AID - 10.1038/cr.2016.101 [doi]
PST - ppublish
SO  - Cell Res. 2016 Oct;26(10):1099-1111. doi: 10.1038/cr.2016.101. Epub 2016 Aug 30.