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bioRxiv · 10.1101/2021.05.04.442585

Haploinsufficiency of the essential gene RpS12 causes defects in erythropoiesis and hematopoietic stem cell maintenance

Folgado Marco, V.·Ames, K.·Gritsman, K.·Baker, N. E.
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Abstract

Ribosomal protein (Rp) gene haploinsufficiency can result in Diamond-Blackfan Anemia (DBA), characterized by defective erythropoiesis and skeletal defects. Some mouse Rp mutations recapitulate DBA phenotypes, although others lack erythropoietic or skeletal defects. We generated a conditional knockout mouse to partially delete RpS12, which results in homozygous embryonic lethality. Rps12+/- mice have growth and morphological defects, pancytopenia and impaired erythropoiesis. A striking reduction in hematopoietic stem cells (HSCs) and progenitors in the bone marrow (BM) was associated with decreased ability to repopulate the blood system after competitive and non-competitive BM transplantation. The mutants exhibited loss of HSC quiescence, which was associated with ERK and MTOR activation and increased global translation in HSC and progenitors. Thus, RpS12 has a very strong requirement in maintaining HSC quiescence and function, in addition to erythropoiesis that is affected in DBA patients.

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Folgado Marco, V., Ames, K., Gritsman, K., Baker, N. E.. 2021-05-04. Haploinsufficiency of the essential gene RpS12 causes defects in erythropoiesis and hematopoietic stem cell maintenance. https://doi.org/10.1101/2021.05.04.442585

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