A transgenic rat expressing green fluorescent protein (GFP) in peripheral nerves provides a new hindlimb model for the study of nerve injury and regeneration.
In order to evaluate nerve regeneration in clinically relevant hindlimb surgical paradigms not feasible in fluorescent mice models, we developed a rat that expresses green fluorescent protein (GFP) in neural tissue.



Transgenic Sprague-Dawley rat lines were created using pronuclear injection of a transgene expressing GFP under the control of the thy1 gene. Nerves were imaged under fluorescence microscopy and muscles were imaged with confocal microscopy to determine GFP expression following sciatic nerve crush, transection and direct suturing, and transection followed by repair with a nerve isograft from nonexpressing littermates.



In each surgical paradigm, fluorescence microscopy demonstrated the loss and reappearance of fluorescence with regeneration of axons following injury. Nerve regeneration was confirmed with imaging of Wallerian degeneration followed by reinnervation of extensor digitorum longus (EDL) muscle motor endplates using confocal microscopy.



The generation of a novel transgenic rat model expressing GFP in neural tissue allows in vivo imaging of nerve regeneration and visualization of motor endplate reinnervation. This rat provides a new model for studying peripheral nerve injury and regeneration over surgically relevant distances.
Division of Plastic and Reconstructive Surgery, Department of Surgery, Washington University School of Medicine, St. Louis, MO 63110, USA.
Amy M
AM
Moore
The Hospital for Sick Children Division of Plastic and Reconstructive Surgery, Toronto, Canada M5G1X8; University of Toronto Department of Surgery, Toronto, Canada M5G1X8; University of Toronto Institute of Biomaterials and Biomedical Engineering, Toronto, Canada M5G1X8.
Gregory H
GH
Borschel
Division of Plastic and Reconstructive Surgery, Department of Surgery, Washington University School of Medicine, St. Louis, MO 63110, USA.
Katherine B
KB
Santosa
Division of Plastic and Reconstructive Surgery, Department of Surgery, Washington University School of Medicine, St. Louis, MO 63110, USA.
Eric R
ER
Flagg
Division of Plastic and Reconstructive Surgery, Department of Surgery, Washington University School of Medicine, St. Louis, MO 63110, USA.
Alice Y
AY
Tong
Division of Plastic and Reconstructive Surgery, Department of Surgery, Washington University School of Medicine, St. Louis, MO 63110, USA.
Rahul
R
Kasukurthi
Division of Plastic and Reconstructive Surgery, Department of Surgery, Washington University School of Medicine, St. Louis, MO 63110, USA.
Piyaraj
P
Newton
Division of Plastic and Reconstructive Surgery, Department of Surgery, Washington University School of Medicine, St. Louis, MO 63110, USA.
Ying
Y
Yan
Division of Plastic and Reconstructive Surgery, Department of Surgery, Washington University School of Medicine, St. Louis, MO 63110, USA.
Daniel A
DA
Hunter
Division of Plastic and Reconstructive Surgery, Department of Surgery, Washington University School of Medicine, St. Louis, MO 63110, USA.
Philip J
PJ
Johnson
Division of Plastic and Reconstructive Surgery, Department of Surgery, Washington University School of Medicine, St. Louis, MO 63110, USA. Electronic address: mackinnon@wudosis.wustl.edu.
Susan E
SE
Mackinnon
D000818:Animals; D004195:Disease Models, Animal; D049452:Green Fluorescent Proteins / Q000378:metabolism*; D006614:Hindlimb / Q000293:injuries / Q000294:innervation / Q000473:pathology; D009416:Nerve Regeneration / Q000502:physiology*; D059348:Peripheral Nerve Injuries / Q000473:pathology* / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D055647:Rats, Transgenic; D020426:Sciatic Neuropathy / Q000473:pathology* / Q000503:physiopathology*
D049452:Green Fluorescent Proteins