Modeling disease mutations by gene targeting in one-cell mouse embryos
- 12 June 2012
- journal article
- research article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences of the United States of America
- Vol. 109 (24), 9354-9359
- https://doi.org/10.1073/pnas.1121203109
Abstract
Gene targeting by zinc-finger nucleases in one-cell embryos provides an expedite mutagenesis approach in mice, rats, and rabbits. This technology has been recently used to create knockout and knockin mutants through the deletion or insertion of nucleotides. Here we apply zinc-finger nucleases in one-cell mouse embryos to generate disease-related mutants harboring single nucleotide or codon replacements. Using a gene-targeting vector or a synthetic oligodesoxynucleotide as template for homologous recombination, we introduced missense and silent mutations into the Rab38 gene, encoding a small GTPase that regulates intracellular vesicle trafficking. These results demonstrate the feasibility of seamless gene editing in one-cell embryos to create genetic disease models and establish synthetic oligodesoxynucleotides as a simplified mutagenesis tool.Keywords
This publication has 37 references indexed in Scilit:
- Knockout rats generated by embryo microinjection of TALENsNature Biotechnology, 2011
- Targeted Genome Modification in Mice Using Zinc-Finger NucleasesGenetics, 2010
- The Human Gene Mutation Database: 2008 updateGenome Medicine, 2009
- A data‐mining approach to rank candidate protein‐binding partners—The case of biogenesis of lysosome‐related organelles complex‐1 (BLOC‐1)Journal of Inherited Metabolic Disease, 2008
- Targeted gene knockout in mammalian cells by using engineered zinc-finger nucleasesProceedings of the National Academy of Sciences of the United States of America, 2008
- Melanosome Maturation Defect in Rab38-deficient Retinal Pigment Epithelium Results in Instability of Immature Melanosomes during Transient MelanogenesisMolecular Biology of the Cell, 2007
- Rab38 and Rab32 control post-Golgi trafficking of melanogenic enzymesThe Journal of cell biology, 2006
- Hermansky–Pudlak syndrome: a disease of protein trafficking and organelle functionPigment Cell Research, 2006
- The Cell Biology of Hermansky–Pudlak Syndrome: Recent AdvancesTraffic, 2005
- Expression and characterization of Rab38, a new member of the Rab small G protein familyBiological Chemistry, 2005