Abstract | BACKGROUND: METHODS: rAAV containing the mouse LCAD cDNA (mLCAD) under the transcriptional control of the CMV/chicken beta-actin hybrid promoter were injected intramuscularly into the tibialis anterior (TA) muscle of LCAD(+/-) mice or injected into the portal vein to transduce hepatocytes. RESULTS: Ten weeks post-injection of rAAV1-mLCAD into the TA muscle, significantly increased levels of mLCAD within mitochondria were demonstrated by immunostaining of TA sections, immunoblotting of mitochondrial isolates and by the electron transfer flavoprotein (ETF) fluorescence reduction enzyme activity assay. Magnetic resonance spectroscopy of vector-injected TA muscle demonstrated a reduction in the lipid content compared to phosphate-buffered saline-injected mice, whereas a systemic effect was observed as a reduction in liver macrosteatosis. Eight weeks after portal vein injection of rAAV8-mLCAD into LCAD(+/-) mice, increased levels of mLCAD within hepatocyte mitochondria were demonstrated by immunostaining and also by the ETF assay. Scoring of the hepatosteatosis observed in partially deficient LCAD mice indicated a reduction in the lipid content within livers of vector-treated mice. CONCLUSIONS: These studies show that rAAV-mediated delivery of mLCAD was efficient and led to an amelioration of local and systemic pathologies observed in partially deficient LCAD mice.
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Authors | Stuart G Beattie, Eric Goetzman, Qiuishi Tang, Thomas Conlon, Martha Campbell-Thompson, Dietrich Matern, Jerry Vockley, Terence R Flotte |
Journal | The journal of gene medicine
(J Gene Med)
Vol. 10
Issue 10
Pg. 1113-23
(Oct 2008)
ISSN: 1521-2254 [Electronic] England |
PMID | 18720429
(Publication Type: Journal Article, Research Support, N.I.H., Extramural)
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Copyright | Copyright (c) 2008 John Wiley & Sons, Ltd. |
Chemical References |
- Acyl-CoA Dehydrogenase, Long-Chain
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Topics |
- Acyl-CoA Dehydrogenase, Long-Chain
(deficiency, genetics, metabolism)
- Animals
- Dependovirus
(genetics, metabolism)
- Female
- Gene Transfer Techniques
- Genetic Vectors
(administration & dosage)
- Liver
(metabolism)
- Male
- Mice
- Transduction, Genetic
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