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Generation of a Mouse Model Lacking the Non-Homologous End-Joining Factor Mri/Cyren

Sergio Castañeda-Zegarra1,2, Camilla Huse1,2, Øystein Røsand1,2

  • 1Department of Clinical and Molecular Medicine (IKOM), Norwegian University of Science and Technology, 7491 Trondheim, Norway.

Biomolecules
|December 5, 2019
PubMed

Insights

The Mri/Cyren protein is largely dispensable for DNA repair and mouse development, despite its role in non-homologous end joining (NHEJ) pathway. Mice lacking Mri showed reduced B cell class switch recombination and slower neuronal progenitor proliferation.

Area of Science:

  • Molecular Biology
  • Genetics
  • Immunology

Background:

  • Non-homologous end joining (NHEJ) is crucial for repairing DNA double-strand breaks (DSBs) and is essential for lymphocyte development and function.
  • Mutations in NHEJ pathway genes can lead to neurological and immunodeficiency disorders.
  • Mri/Cyren is an accessory factor in the NHEJ pathway, but its precise physiological role remains unclear.

Purpose of the Study:

  • To investigate the physiological role of Mri/Cyren in DNA repair and mouse development.
  • To determine if Mri/Cyren deficiency impacts V(D)J recombination or class switch recombination.
  • To assess the impact of Mri/Cyren deficiency on neuronal progenitor proliferation.

Main Methods:

  • Generated a frame-shift mutation in the Mri gene in mice to create Mri-deficient models.
  • Analyzed the development and immune cell function of Mri-deficient mice compared to wild-type and immunodeficient controls.
  • Assessed DNA double-strand break sensitivity in human cell lines lacking Mri.

Main Results:

  • Mri-deficient mice exhibited reduced class switch recombination in B lymphocytes.
  • Neuronal progenitors showed slower proliferation in Mri-deficient mice compared to wild-type littermates.
  • Human cell lines lacking Mri displayed similar sensitivity to DSBs as wild-type controls, suggesting Mri/Cyren is not essential for DNA repair in these cells.

Conclusions:

  • Mri/Cyren plays a role in B cell class switch recombination and neuronal progenitor proliferation.
  • Despite its involvement in the NHEJ pathway, Mri/Cyren appears largely dispensable for overall DNA repair and mouse development.
  • The accessory factors in the NHEJ pathway may have context-dependent roles and varying levels of dispensability.
Keywords:
NHEJdouble-strand breakslymphocytemouse modelneurodevelopment

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