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Maternal effect for DNA mismatch repair in the mouse
Vanessa E Gurtu1, Shelly Verma, Allie H Grossmann
1Department of Nutritional Sciences and Toxicology, University of California, Berkeley, California 94720, USA.
Genetics
|January 24, 2002
Summary
Maternal deficiency in DNA mismatch repair (DMR) causes microsatellite instability (MSI) in female germ lines and surprisingly in paternal alleles due to early embryonic errors. This highlights Pms2 deficiency as a maternal effect impacting genome stability.
Area of Science:
- Genetics
- Molecular Biology
- Genomics
Background:
- DNA mismatch repair (DMR) is crucial for maintaining genome stability.
- Deficiency in DMR leads to microsatellite instability (MSI), characterized by alterations in repeat lengths at microsatellite sequences.
- Mice lacking Pms2, a key DMR gene, exhibit MSI and develop cancer.
Purpose of the Study:
- To investigate the impact of maternal DNA mismatch repair deficiency on genetic stability.
- To analyze the consequences of Pms2 deficiency in female mice on their offspring's genome.
Main Methods:
- Analysis of F(1) progeny from Pms2(-/-) female mice mated with wild-type males.
- Examination of microsatellite instability (MSI) in offspring derived from maternal DMR deficiency.
Main Results:
- Maternal Pms2 deficiency resulted in approximately 9% MSI in the female germ line.
- Unexpectedly, MSI was also detected in paternal alleles, despite the wild-type status of the male parent.
- This suggests a maternal effect causing mosaicism for paternal alleles due to Pms2 deficiency in early embryonic divisions.
Conclusions:
- Pms2 deficiency acts as a maternal effect, leading to postzygotic mutations in early mouse embryos.
- The absence of DMR in one-cell embryos allows unrepaired replication errors to propagate.
- This study identifies the first DNA repair gene deficiency to manifest as a maternal effect in mice, impacting genome stability.