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Detected microsatellite polymorphisms in genetically altered inbred mouse strains.
Xiaoyan Du1, Jing Cui, Chao Wang
1Department of Laboratory Animal Science, School of Basic Medical Science, Capital Medical University, Beijing, 100069, China.
Molecular Genetics and Genomics : MGG
|May 24, 2013
Summary
Genetic modifications like gene knockout, transgenes, or chemical mutagens can cause changes in microsatellite DNA. Specific microsatellite loci act as mutation hotspots, useful for monitoring genetic changes in modified mice.
Area of Science:
- Genomics and Molecular Biology
- Mammalian Genetics
- DNA Mutation Studies
Background:
- Microsatellites are repetitive DNA sequences sensitive to genetic alterations.
- Previous studies showed microsatellite genotype changes (CMPs) in gene knockout (KO) mice.
- The effect of transgene (Tg) insertion or chemical mutagenesis (ENU) on microsatellites was unknown.
Purpose of the Study:
- To investigate if transgene insertion or N-ethyl-N-nitrosourea (ENU) treatment induces microsatellite mutations.
- To compare microsatellite mutation patterns across different genetic modification methods (KO, Tg, ENU).
Main Methods:
- Examined 198 microsatellite loci across chromosomes in six Tg mouse strains using polymerase chain reaction (PCR).
- Compared Tg mice microsatellite sequences with background strains to identify genotype changes (CMPs).
- Used spontaneously mutated mice as negative controls and analyzed ENU-mutated mice for CMPs.
Main Results:
- 40 out of 198 (20.2%) microsatellite loci showed CMPs in Tg mice.
- Four loci (D11mit258, D13mit3, D14mit102, DXmit172) were shared between Tg and KO mice.
- One locus (D14mit102) exhibited CMPs across all three genetic modification types (Tg, ENU, KO).
Conclusions:
- Genetic modifications (KO, Tg, ENU) induce microsatellite genotype changes (CMPs) in mice.
- Specific microsatellite loci are 'hot spots' for mutations induced by genetic modification.
- These hot spots can serve as markers for genetic monitoring in genetically modified mouse models.
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