The R229Q mutation of Rag2 does not characterize severe immunodeficiency in mice

Young Jin, Ara Lee, Ja Hyun Oh, Han Woong Lee, Sang Jun Ha

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3 Citations (Scopus)


RAG1 or RAG2 mutations are associated with defects in V(D)J recombination activity, causing severe immunodeficiency with a wide spectrum of clinical phenotypes. A R229Q mutation of RAG2 was identified in patients with severe combined immunodeficiency (SCID) or Omenn syndrome (OS). Although some factors determining the clinical features between SCID and OS were not clear, the molecular mechanism of OS was studied in a mouse model in which an EGFP tag is fused to Rag2 with the R229Q mutation. To design the human disease model mimicking severe immunodeficiency, we generated Rag2-R229Q knock-in mice without an epitope tag. Mutant mice showed impaired T and B cell differentiation with reduced V(D)J recombination activity; however, the extent to which the R229Q mutation affects severe immunodeficiency was not severe. While Rag2-R229Q mutation under some conditions may cause severe immunological and clinical phenotypes similar to human SCID or OS, R229Q mutation per se did not cause severe immunodeficiency in mice, suggesting that additional factors other than R229Q mutation are required to induce severe immunodeficiency. Thus, our report implies that the effects of genetic background and/or a tagged protein sequence may alter the mouse immune system, revealing the mechanism of phenotypic heterogeneity arising from an identical mutation.

Original languageEnglish
Article number4415
JournalScientific reports
Issue number1
Publication statusPublished - 2019 Dec 1

Bibliographical note

Funding Information:
This work was supported by grants from the National Research Foundation of Korea (NRF) funded by the Korean government (MEST; 2018R1A2A1A05022746, 2017R1A4A1015328, 2018M3A9H3024850, 2018R1A2A1A05076997). and the Korea Food and Drug Administration (14182MFDS978).

Publisher Copyright:
© 2019, The Author(s).

All Science Journal Classification (ASJC) codes

  • General


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