title: Genome instability and embryonic developmental defects in RMI1 deficient mice.
abstract: RMI1 forms an evolutionarily conserved complex with BLM/TOP3α/RMI2 (BTR complex) to prevent and resolve aberrant recombination products, thereby promoting genome stability. Most of our knowledge about RMI1 function has been obtained from biochemical studies in vitro. In contrast, the role of RMI1 in vivo remains unclear. Previous attempts to generate an Rmi1 knockout mouse line resulted in pre-implantation embryonic lethality, precluding the use of mouse embryonic fibroblasts (MEFs) and embryonic morphology to assess the role of RMI1 in vivo. Here, we report the generation of an Rmi1 deficient mouse line (hy/hy) that develops until 9.5 days post coitum (dpc) with marked defects in development. MEFs derived from Rmi1(hy/hy) are characterized by severely impaired cell proliferation, frequently having elevated DNA content, high numbers of micronuclei and an elevated percentage of partial condensed chromosomes. Our results demonstrate the importance of RMI1 in maintaining genome integrity and normal embryonic development.
authors.affiliation: Cell Cycle and Cancer Biology Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA.
authors.forename: Michel F
authors.initials: MF
authors.lastname: Guiraldelli
authors.forename: Craig
authors.initials: C
authors.lastname: Eyster
authors.forename: Roberto J
authors.initials: RJ
authors.lastname: Pezza
mesh_terms: D000818:Animals; D017209:Apoptosis; D002352:Carrier Proteins / Q000235:genetics* / Q000502:physiology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D053903:DNA Breaks, Double-Stranded; D004260:DNA Repair; D004268:DNA-Binding Proteins; D047108:Embryonic Development / Q000235:genetics / Q000502:physiology; D053595:Embryonic Stem Cells; D005260:Female; D042822:Genomic Instability; D008264:Macrophages / Q000166:cytology / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008940:Mitotic Index; D009687:Nuclear Proteins / Q000172:deficiency / Q000235:genetics* / Q000502:physiology*
chemical_list: D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; C555770:RMI1 protein, mouse
keywords: DNA repair; Genome instability; Homologous recombination
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