PMID- 27793099
OWN - NLM
STAT- MEDLINE
DCOM- 20170821
LR  - 20181113
IS  - 1471-2202 (Electronic)
IS  - 1471-2202 (Linking)
VI  - 17
IP  - 1
DP  - 2016 Oct 28
TI  - Severe respiratory changes at end stage in a FUS-induced disease state in adult 
      rats.
PG  - 69
LID - 69
AB  - BACKGROUND: Fused in sarcoma (FUS) is an RNA-binding protein associated with the 
      neurodegenerative diseases amyotrophic lateral sclerosis (ALS) and frontotemporal 
      lobar degeneration. ALS manifests in patients as a progressive paralysis which 
      leads to respiratory dysfunction and failure, the primary cause of death in ALS. 
      We expressed human FUS in rats to determine if FUS would induce ALS relevant 
      respiratory changes to serve as an early stage disease indicator. The FUS 
      expression was initiated in adult rats by way of an intravenously administered 
      adeno-associated virus vector serotype 9 (AAV9) providing an adult onset model. 
      RESULTS: The rats developed progressive motor impairments observed as early as 
      2-3 weeks post gene transfer. Respiratory abnormalities manifested 4-7 weeks post 
      gene transfer including increased respiratory frequency and decreased tidal 
      volume. Rats with breathing abnormalities also had arterial blood acidosis. 
      Similar detailed plethysmographic changes were found in adult rats injected with 
      AAV9 TDP-43. FUS gene transfer to adult rats yielded a consistent pre-clinical 
      model with relevant motor paralysis in the early to middle stages and respiratory 
      dysfunction at the end stage. Both FUS and TDP-43 yielded a similar consistent 
      disease state. CONCLUSIONS: This modeling method yields disease relevant motor 
      and respiratory changes in adult rats. The reproducibility of the data supports 
      the use of this method to study other disease related genes and their 
      combinations as well as a platform for disease modifying interventional 
      strategies.
FAU - Jackson, Kasey L
AU  - Jackson KL
AD  - Department of Pharmacology, Toxicology, and Neuroscience, Louisiana State 
      University Health Sciences Center, 1501 Kings Hwy, Shreveport, LA, 71130, USA. 
      kjac12@lsuhsc.edu.
FAU - Dhaibar, Hemangini A
AU  - Dhaibar HA
AD  - Department of Cellular Biology and Anatomy, Louisiana State University Health 
      Sciences Center, 1501 Kings Hwy, Shreveport, LA, 71130, USA.
FAU - Dayton, Robert D
AU  - Dayton RD
AD  - Department of Pharmacology, Toxicology, and Neuroscience, Louisiana State 
      University Health Sciences Center, 1501 Kings Hwy, Shreveport, LA, 71130, USA.
FAU - Cananzi, Sergio G
AU  - Cananzi SG
AD  - Department of Cellular Biology and Anatomy, Louisiana State University Health 
      Sciences Center, 1501 Kings Hwy, Shreveport, LA, 71130, USA.
FAU - Mayhan, William G
AU  - Mayhan WG
AD  - Department of Cellular Biology and Anatomy, Louisiana State University Health 
      Sciences Center, 1501 Kings Hwy, Shreveport, LA, 71130, USA.
FAU - Glasscock, Edward
AU  - Glasscock E
AD  - Department of Cellular Biology and Anatomy, Louisiana State University Health 
      Sciences Center, 1501 Kings Hwy, Shreveport, LA, 71130, USA.
FAU - Klein, Ronald L
AU  - Klein RL
AD  - Department of Pharmacology, Toxicology, and Neuroscience, Louisiana State 
      University Health Sciences Center, 1501 Kings Hwy, Shreveport, LA, 71130, USA.
LA  - eng
GR  - K99 HL107641/HL/NHLBI NIH HHS/United States
GR  - R00 HL107641/HL/NHLBI NIH HHS/United States
GR  - R21 NS089397/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20161028
PL  - England
TA  - BMC Neurosci
JT  - BMC neuroscience
JID - 100966986
RN  - 0 (FUS protein, human)
RN  - 0 (RNA-Binding Protein FUS)
RN  - 147336-22-9 (Green Fluorescent Proteins)
SB  - IM
MH  - Acidosis/physiopathology
MH  - Amyotrophic Lateral Sclerosis/complications/*physiopathology
MH  - Animals
MH  - Dependovirus/genetics
MH  - *Disease Models, Animal
MH  - Disease Progression
MH  - Escape Reaction/physiology
MH  - Female
MH  - Genetic Vectors
MH  - Green Fluorescent Proteins/genetics/metabolism
MH  - HEK293 Cells
MH  - Humans
MH  - Hypoxia/physiopathology
MH  - Motor Activity/physiology
MH  - Muscle Strength/physiology
MH  - Paralysis/physiopathology
MH  - RNA-Binding Protein FUS/genetics/*metabolism
MH  - Rats, Sprague-Dawley
MH  - Respiration
MH  - Respiration Disorders/etiology/*physiopathology
MH  - Transfection
PMC - PMC5086065
OTO - NOTNLM
OT  - Adeno-associated virus
OT  - Amyotrophic lateral sclerosis
OT  - FUS
OT  - Gene therapy
OT  - Respiration
OT  - TDP-43
EDAT- 2016/10/30 06:00
MHDA- 2017/08/22 06:00
PMCR- 2016/10/28
CRDT- 2016/10/30 06:00
PHST- 2016/05/11 00:00 [received]
PHST- 2016/10/19 00:00 [accepted]
PHST- 2016/10/30 06:00 [pubmed]
PHST- 2017/08/22 06:00 [medline]
PHST- 2016/10/30 06:00 [entrez]
PHST- 2016/10/28 00:00 [pmc-release]
AID - 10.1186/s12868-016-0304-5 [pii]
AID - 304 [pii]
AID - 10.1186/s12868-016-0304-5 [doi]
PST - epublish
SO  - BMC Neurosci. 2016 Oct 28;17(1):69. doi: 10.1186/s12868-016-0304-5.