Targeted mutation of the DNA methyltransferase gene results in embryonic lethality

@article{Li1992TargetedMO,
  title={Targeted mutation of the DNA methyltransferase gene results in embryonic lethality},
  author={En Li and Timothy H Bestor and Rudolf Jaenisch},
  journal={Cell},
  year={1992},
  volume={69},
  pages={915-926}
}
Complementation of methylation deficiency in embryonic stem cells by a DNA methyltransferase minigene.
TLDR
An amino-terminal domain of the mammalian MTase that is crucial for stable expression and function in vivo is defined and shown by functional rescue of Dnmt mutant embryonic stem cells that contain highly demethylated genomic DNA and fail to differentiate normally.
De novo DNA cytosine methyltransferase activities in mouse embryonic stem cells.
TLDR
A null mutation of the only known mammalian DNA methyltransferase gene is generated in mouse embryonic stem cells and it is found that the development of the homozygous embryos is arrested prior to the 8-somite stage, suggesting the existence of a second DNA methyl transferase in mammalian cells.
A Mouse Model for the Overexpression of Methyltransferases
TLDR
The ubiquitous overexpression of Dnmt1s was investigated in cross-ins that carry the recombined version of the DnMT1s transgene and express RGS-His-tagged DNmt1 as verified by RT-PCR.
Mismatch repair genes identified using genetic screens in Blm-deficient embryonic stem cells
TLDR
The combination of insertional mutagenesis in Blm-deficient ES cells establishes a new approach for phenotype-based recessive genetic screens in ES cells, and demonstrates the recovery of cells with homozygous mutations in known and novel MMR genes.
DNA Damage, Homology-Directed Repair, and DNA Methylation
TLDR
The data support a mechanistic link between HR and DNA methylation and suggest thatDNA methylation in eukaryotes marks homologous recombined segments.
Hypomorphic mutation in hnRNP U results in post-implantation lethality
TLDR
An embryonic lethal mutation induced by insertion of the U3Neo gene trap retrovirus into an intron of the gene encoding heterogeneous ribonuclear protein U (Hnrnpu) is characterized, suggesting that nearly wild-type levels of hnRNP U are required for embryonic development.
Dnmt 1 deficiency leads to enhanced microsatellite instability in mouse embryonic stem cells
TLDR
A model system to analyze the effects of DNA methyltransferase 1 (Dnmt1) deficiency on DNA mismatch repair (MMR) in mouse embryonic stem (ES) cells found that DnMT1 deficiency led to a 7-fold increase in the microsatellite slippage rate.
A method for the generation of conditional gene repair mutations in mice.
TLDR
A method for the generation of conditional gene repair mutations that employs a loxP-flanked (floxed) selectable marker and transcriptional/translational stop cassette (neostop) located within the first intron of a target gene.
Transcription influences repair-induced DNA methylation
TLDR
A genetic system that allows a rapid assessment of homologous-directed repair (HR) of an unique DNA double strand break (DSB) of HeLa or mouse embryonic stem (ES) cells using the I-SceI restriction endonuclease is developed.
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