Maternal effect for DNA mismatch repair in the mouse

Vanessa E. Gurtu, Shelly Verma, Allie H. Grossmann, Robert (Mike) Liskay, William C. Skarnes, Sean M. Baker

Research output: Contribution to journalArticle

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Abstract

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 ∼10% was observed. To determine the consequences of maternal DMR deficiency on genetic stability, we analyzed F1 progeny from Pms2-1- female mice mated with wild-type males. Our analysis indicates that MSI in the female germ line was ∼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.

Original languageEnglish (US)
Pages (from-to)271-277
Number of pages7
JournalGenetics
Volume160
Issue number1
StatePublished - 2002

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DNA Mismatch Repair
Microsatellite Instability
Embryonic Structures
Alleles
Germ Cells
DNA Repair-Deficiency Disorders
Prokaryotic Cells
Mosaicism
Zygote
Genomic Instability
Eukaryotic Cells
DNA Repair
Cell Division
Microsatellite Repeats
Mothers
Maternal Inheritance
Phenotype
Mutation
Genes
Neoplasms

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Gurtu, V. E., Verma, S., Grossmann, A. H., Liskay, R. M., Skarnes, W. C., & Baker, S. M. (2002). Maternal effect for DNA mismatch repair in the mouse. Genetics, 160(1), 271-277.

Maternal effect for DNA mismatch repair in the mouse. / Gurtu, Vanessa E.; Verma, Shelly; Grossmann, Allie H.; Liskay, Robert (Mike); Skarnes, William C.; Baker, Sean M.

In: Genetics, Vol. 160, No. 1, 2002, p. 271-277.

Research output: Contribution to journalArticle

Gurtu, VE, Verma, S, Grossmann, AH, Liskay, RM, Skarnes, WC & Baker, SM 2002, 'Maternal effect for DNA mismatch repair in the mouse', Genetics, vol. 160, no. 1, pp. 271-277.
Gurtu VE, Verma S, Grossmann AH, Liskay RM, Skarnes WC, Baker SM. Maternal effect for DNA mismatch repair in the mouse. Genetics. 2002;160(1):271-277.
Gurtu, Vanessa E. ; Verma, Shelly ; Grossmann, Allie H. ; Liskay, Robert (Mike) ; Skarnes, William C. ; Baker, Sean M. / Maternal effect for DNA mismatch repair in the mouse. In: Genetics. 2002 ; Vol. 160, No. 1. pp. 271-277.
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AU - Baker, Sean M.

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