Maternal Effect for DNA Mismatch Repair in the Mouse

DNA mismatch repair (DMR) functions to maintain genome stability. Prokaryotic and eukaryotic cells deficient in DMR show a microsatellite instability (MSI) phenotype characterized by repeat length alterations at microsatellite sequences. Mice deficient in Pms2, a mammalian homolog of bacterial mutL,...

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Bibliographic Details
Published in:	Genetics (Austin) Vol. 160; no. 1; pp. 271 - 277
Main Authors:	Gurtu, Vanessa E, Verma, Shelly, Grossmann, Allie H, Liskay, R. Michael, Skarnes, William C, Baker, Sean M
Format:	Journal Article
Language:	English
Published:	United States Genetics Soc America 01-01-2002 Genetics Society of America
Subjects:	Adenosine Triphosphatases - genetics Adenosine Triphosphatases - physiology Animals Base Pair Mismatch Crosses, Genetic Deoxyribonucleic acid DNA DNA Repair DNA Repair Enzymes DNA-Binding Proteins - genetics DNA-Binding Proteins - physiology Female Genetics Male Mice Mice, Inbred C57BL Microsatellite Repeats mismatch repair Mismatch Repair Endonuclease PMS2 Mosaicism - genetics Mutation mutL gene Pms2 gene Rodents
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Summary:	DNA mismatch repair (DMR) functions to maintain genome stability. Prokaryotic and eukaryotic cells deficient in DMR show a microsatellite instability (MSI) phenotype characterized by repeat length alterations at microsatellite sequences. Mice deficient in Pms2, a mammalian homolog of bacterial mutL, develop cancer and display MSI in all tissues examined, including the male germ line where a frequency of approximately 10% was observed. To determine the consequences of maternal DMR deficiency on genetic stability, we analyzed F(1) progeny from Pms2(-/-) female mice mated with wild-type males. Our analysis indicates that MSI in the female germ line was approximately 9%. MSI was also observed in paternal alleles, a surprising result since the alleles were obtained from wild-type males and the embryos were therefore DMR proficient. We propose that mosaicism for paternal alleles is a maternal effect that results from Pms2 deficiency during the early cleavage divisions. The absence of DMR in one-cell embryos leads to the formation of unrepaired replication errors in early cell divisions of the zygote. The occurrence of postzygotic mutation in the early mouse embryo suggests that Pms2 deficiency is a maternal effect, one of a limited number identified in the mouse and the first to involve a DNA repair gene.
Bibliography:	ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23
ISSN:	0016-6731 1943-2631 1943-2631
DOI:	10.1093/genetics/160.1.271