PMID- 28872135
OWN - NLM
STAT- MEDLINE
DCOM- 20180514
LR  - 20181202
IS  - 1940-087X (Electronic)
IS  - 1940-087X (Linking)
IP  - 126
DP  - 2017 Aug 25
TI  - Methods and Tips for Intravenous Administration of Adeno-associated Virus to Rats 
      and Evaluation of Central Nervous System Transduction.
LID - 10.3791/55994 [doi]
LID - 55994
AB  - Adeno-associated virus (AAV) vectors are a key reagent in the neurosciences for 
      clustered regularly interspaced short palindromic repeats (CRISPR), optogenetics, 
      cre-lox targeting, etc. The purpose of this manuscript is to aid the investigator 
      attempting expansive central nervous system (CNS) gene transfer in the rat via 
      tail vein injection of AAV. Wide-scale expression is relevant for conditions with 
      widespread pathology, and a rat model is significant due to its greater size and 
      physiologic similarities to humans compared to mice. In this example application, 
      a wide-scale neuronal transduction is used to mimic a neurodegenerative disease 
      that affects the entire spinal cord, amyotrophic lateral sclerosis (ALS). The 
      efficient wide-scale CNS transduction can also be used to deliver therapeutic 
      protein factors in pre-clinical studies. After a post-injection expression 
      interval of several weeks, the effects of the transduction are evaluated. For a 
      green fluorescent protein (GFP) control vector, the amount of GFP in the 
      cerebellum is estimated quickly and reliably by a basic imaging program. For 
      motor disease phenotypes that are induced by the ALS related protein transactive 
      response DNA-binding protein of 43 kDa (TDP-43), the deficits are scored by 
      escape reflex and rotarod. Beyond disease modeling and gene therapy, there are 
      diverse potential applications for the wide-scale gene targeting described here. 
      The expanded use of this method will aid in expediting hypothesis testing in the 
      neurosciences and neurogenetics.
FAU - Grames, Mychal S
AU  - Grames MS
AD  - Department of Pharmacology, Toxicology, and Neuroscience, Louisiana State 
      University Health Sciences Center.
FAU - Jackson, Kasey L
AU  - Jackson KL
AD  - Department of Pharmacology, Toxicology, and Neuroscience, Louisiana State 
      University Health Sciences Center.
FAU - Dayton, Robert D
AU  - Dayton RD
AD  - Department of Pharmacology, Toxicology, and Neuroscience, Louisiana State 
      University Health Sciences Center.
FAU - Stanford, John A
AU  - Stanford JA
AD  - Department of Molecular & Integrative Physiology, University of Kansas Medical 
      Center.
FAU - Klein, Ronald L
AU  - Klein RL
AD  - Department of Pharmacology, Toxicology, and Neuroscience, Louisiana State 
      University Health Sciences Center; Klein@lsuhsc.edu.
LA  - eng
GR  - P20 GM103418/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Video-Audio Media
DEP - 20170825
PL  - United States
TA  - J Vis Exp
JT  - Journal of visualized experiments : JoVE
JID - 101313252
SB  - IM
MH  - Administration, Intravenous
MH  - Amyotrophic Lateral Sclerosis/*genetics/metabolism
MH  - Animals
MH  - Central Nervous System/*metabolism
MH  - Female
MH  - *Gene Transfer Techniques
MH  - Genetic Vectors/*administration & dosage/*genetics
MH  - Humans
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Transduction, Genetic
PMC - PMC5614388
EDAT- 2017/09/06 06:00
MHDA- 2018/05/15 06:00
PMCR- 2018/08/25
CRDT- 2017/09/06 06:00
PHST- 2017/09/06 06:00 [entrez]
PHST- 2017/09/06 06:00 [pubmed]
PHST- 2018/05/15 06:00 [medline]
PHST- 2018/08/25 00:00 [pmc-release]
AID - 55994 [pii]
AID - 10.3791/55994 [doi]
PST - epublish
SO  - J Vis Exp. 2017 Aug 25;(126):55994. doi: 10.3791/55994.