Rat strain differences in the ectopic osteogenic potential of recombinant human BMP adenoviruses.
Different animal strains have different genetic backgrounds that influence their physiological function and pathological process. The differences in genetic background may affect the efficiency of adenoviral infection and target gene expression and further cause different gene therapy results when target genes are delivered with adenoviral vectors. In this study, ectopic bone was not seen in ADCMVBMP4 injection sites, but was formed in ADCMVBMP9 injection sites in all rat strains. The mean volumes of bone induced with ADCMVBMP9 were 0.87 +/- 0.2 cm3 in Wistar, 0.26 +/- 0.1 cm3 in Long-Evans, 0.34 +/- 0.2 cm3 in Sprague-Dawley, 0.44 +/- 0.1 cm3 in ACI, 0.66 +/- 0.2 cm3 in PVG, and 0.58 +/- 0.1 cm3 in Fischer 344 rats. This indicates that ADCMVBMP9 has different bone formation potentials in different immunocompetent rat strains (P = 0.02). The basic levels of CD4+ and CD8+ T cells in blood before viral infection and titers of adenoviral neutralizing antibodies 30 days post-viral infection were significantly different among rat strains (P < 0.01). The efficiencies of target gene expression delivered with adenovirus were also significantly different in primary muscle cell cultures from different rat strains (P < 0.01). The different osteogenic potentials of ADCMVBMP9 among rat strains may be, in part, due to the differences in immune factors and target gene expression efficiency in muscle tissue.
Molecular Neurosurgery Lab, Department of Neurosurgery, University of Virginia Health System, Charlottesville, VA 22908, USA.
Jin Zhong
JZ
Li
Hongwei
H
Li
Brad
B
Dunford
David
D
Holman
Brian
B
Beres
Debra D
DD
Pittman
Gerald R
GR
Hankins
Gregory A
GA
Helm
D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000235:genetics*; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D002454:Cell Differentiation; D005822:Genetic Vectors; D055427:Growth Differentiation Factor 2; D055412:Growth Differentiation Factors; D008156:Luciferases / Q000378:metabolism; D009132:Muscles / Q000166:cytology; D009857:Oncogenes; D051381:Rats; D011916:Rats, Inbred F344; D020318:Rats, Long-Evans; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D013045:Species Specificity; D014056:Tomography, X-Ray
D019485:Bone Morphogenetic Proteins; C525887:GDF2 protein, human; D055427:Growth Differentiation Factor 2; D055412:Growth Differentiation Factors; D008156:Luciferases