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Updated: Jun 12, 2026
Cell Type-specific Gene Expression Profiling in the Mouse Liver
Published on: September 17, 2019
High volume naked DNA tail-vein injection restores liver function in Fah-knock out mice
Elke Eggenhofer1, Axel Doenecke, Philipp Renner
1Department of Surgery, University Medical Center Regensburg, Regensburg, Germany.
Background:
Despite pharmaceutical treatment with NTBC (2-2-nitro-4-fluoromethylbenzoyl-1,3-cyclohexanedione), a high incidence of liver malignancies occur in humans and mice suffering from hereditary tyrosinemia type 1 (HT1) caused by mutation of the fumarylacetoacetate hydrolase (fah) gene.
Methods:
To evaluate the efficacy of a definitive treatment for HT1, we transfected fah knockout mice with naked plasmid DNA using high volume tail-vein injection. This approach was chosen to reduce the occurrence of insertional mutagenesis that is frequently observed when using other (retro-)viral vectors. To prolong gene expression, the fah gene was cloned between adeno-associated virus (AAV)-specific inverted terminal repeats (ITRs).
Results:
All animals treated with high volume plasmid DNA injections could be successfully weaned off NTBC and survived in the long term without any further pharmacological support. Up to 50% fah positive hepatocytes were detected in livers of naked plasmid DNA-treated animals and serum liver function tests approximated those of wild-type controls.
Conclusions:
Naked plasmid DNA transfection offers a promising alternative treatment for HT1. Minimizing side-effects makes this approach especially appealing.
