Differential short-term transduction efficiency of adult versus newborn mouse tissues by adenoviral recombinants.
We demonstrated different transduction efficiency in several major organs of the immature (newborn) versus mature (adult) mice using adenoviral recombinants containing expression cassettes for either firefly luciferase or bacterial beta-galactosidase reporter genes. The studied tissues included skeletal muscle, heart, brain, lung, kidney, and liver. The transduction efficiency in all tissues, especially skeletal muscle, was significantly less in adults than in newborns, with two exceptions. In the heart, transduction efficiency was the same in newborns and adults, while in brain, it was greater in the adult than in the newborn. The cited differences in transduction efficiencies between newborn and adult tissues applied approximately equally to both reporter genes. The alpha v integrin level showed the same trend as the transduction efficiency in all tissues, except the heart. Polymerase chain reaction showed a specific adenoviral product in proportion to the reporter gene expression in muscle, heart, and brain. The results of this study should be considered in designing gene therapy strategies in genetic diseases.
Montreal Neurological Institute, McGill University, Quebec, Canada.
J
J
Huard
H
H
Lochmüller
G
G
Acsadi
A
A
Jani
P
P
Holland
C
C
Guérin
B
B
Massie
G
G
Karpati
D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D000831:Animals, Newborn / Q000235:genetics; D015703:Antigens, CD / Q000032:analysis; D001483:Base Sequence; D001923:Brain Chemistry; D004279:DNA, Viral / Q000032:analysis; D004587:Electrophoresis, Agar Gel; D004591:Electrophoresis, Polyacrylamide Gel; D018014:Gene Transfer Techniques; D017930:Genes, Reporter / Q000235:genetics; D005822:Genetic Vectors; D039564:Integrin alphaV; D008156:Luciferases / Q000096:biosynthesis / Q000235:genetics; D051379:Mice; D008969:Molecular Sequence Data; D009132:Muscles / Q000737:chemistry; D001616:beta-Galactosidase / Q000096:biosynthesis / Q000235:genetics
D015703:Antigens, CD; D004279:DNA, Viral; D039564:Integrin alphaV; D008156:Luciferases; D001616:beta-Galactosidase