PMID- 22693957
OWN - NLM
STAT- MEDLINE
DCOM- 20130108
LR  - 20211021
IS  - 1946-6544 (Electronic)
IS  - 1946-6536 (Print)
IS  - 1946-6536 (Linking)
VI  - 23
IP  - 2
DP  - 2012 Apr
TI  - Retrograde gene delivery to hypoglossal motoneurons using adeno-associated virus 
      serotype 9.
PG  - 148-56
LID - 10.1089/hgtb.2012.009 [doi]
AB  - Retrograde viral transport (i.e., muscle to motoneuron) enables targeted gene 
      delivery to specific motor pools. Recombinant adeno-associated virus serotype 9 
      (AAV9) robustly infects motoneurons, but the retrograde transport capabilities of 
      AAV9 have not been systematically evaluated. Accordingly, we evaluated the 
      retrograde transduction efficiency of AAV9 after direct tongue injection in 
      129SVE mice as well as a mouse model that displays neuromuscular pathology 
      (Gaa(-/-)). Hypoglossal (XII) motoneurons were histologically evaluated 8 weeks 
      after tongue injection with AAV9 encoding green fluorescent protein (GFP) with 
      expression driven by the chicken beta-actin promoter (1 x 10(11) vector genomes). On 
      average, GFP expression was detected in 234 +/- 43 XII motoneurons 8 weeks after 
      AAV9-GFP tongue injection. In contrast, tongue injection with a highly efficient 
      retrograde anatomical tracer (cholera toxin beta subunit, CT-beta) resulted in 
      infection of 818 +/- 88 XII motoneurons per mouse. The retrograde transduction 
      efficiency of AAV9 was similar between the 129SVE mice and those with 
      neuromuscular disease (Gaa(-/-)). Routine hematoxylin and eosin staining and 
      cluster of differentiation (CD) immunostaining for T cells (CD3) indicated no 
      persistent inflammation within the tongue or XII nucleus after AAV9 injection. 
      Additional experiments indicated no adverse effects of AAV9 on the pattern of 
      breathing. We conclude that AAV9 can retrogradely infect a significant portion of 
      a given motoneuron pool in normal and dystrophic mice, and that its transduction 
      efficiency is approximately 30% of what can be achieved with CT-beta.
FAU - ElMallah, Mai K
AU  - ElMallah MK
AD  - Department of Pediatrics, College of Medicine, University of Florida, 
      Gainesville, FL 32610, USA.
FAU - Falk, Darin J
AU  - Falk DJ
FAU - Lane, Michael A
AU  - Lane MA
FAU - Conlon, Thomas J
AU  - Conlon TJ
FAU - Lee, Kun-Ze
AU  - Lee KZ
FAU - Shafi, Nadeem I
AU  - Shafi NI
FAU - Reier, Paul J
AU  - Reier PJ
FAU - Byrne, Barry J
AU  - Byrne BJ
FAU - Fuller, David D
AU  - Fuller DD
LA  - eng
GR  - 1R01HD052682-01A1/HD/NICHD NIH HHS/United States
GR  - P01 DK58327-03/DK/NIDDK NIH HHS/United States
GR  - P01 HL059412/HL/NHLBI NIH HHS/United States
GR  - 5F32HL095282-02/HL/NHLBI NIH HHS/United States
GR  - UL1 RR029890/RR/NCRR NIH HHS/United States
GR  - HL59412/HL/NHLBI NIH HHS/United States
PT  - Evaluation Study
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PL  - United States
TA  - Hum Gene Ther Methods
JT  - Human gene therapy methods
JID - 101573202
SB  - IM
MH  - Animals
MH  - Dependovirus/*genetics
MH  - Gene Targeting/*methods
MH  - *Gene Transfer Techniques
MH  - Genetic Therapy/*methods
MH  - Genetic Vectors/*genetics
MH  - Hypoglossal Nerve/*cytology
MH  - Mice
MH  - Microscopy, Fluorescence
MH  - Motor Neurons/*metabolism
MH  - Real-Time Polymerase Chain Reaction
PMC - PMC4015220
EDAT- 2012/06/15 06:00
MHDA- 2013/01/09 06:00
PMCR- 2013/04/01
CRDT- 2012/06/15 06:00
PHST- 2012/06/15 06:00 [entrez]
PHST- 2012/06/15 06:00 [pubmed]
PHST- 2013/01/09 06:00 [medline]
PHST- 2013/04/01 00:00 [pmc-release]
AID - 10.1089/hgtb.2012.009 [pii]
AID - 10.1089/hgtb.2012.009 [doi]
PST - ppublish
SO  - Hum Gene Ther Methods. 2012 Apr;23(2):148-56. doi: 10.1089/hgtb.2012.009.