Title

Rasa3 regulates stage-specific cell cycle progression in murine erythropoiesis.

Document Type

Article

Publication Date

3-2021

Keywords

JMG

JAX Source

Blood Cells Mol Dis 2021 Mar; 87:102524

PMID

33341069

DOI

https://doi.org/10.1016/j.bcmd.2020.102524

Grant

HL134043; HL144436; HL152099

Abstract

Inherited bone marrow failure syndromes (IBMFS) are heterogeneous disorders characterized by dysregulated hematopoiesis in various lineages, developmental anomalies, and predisposition to malignancy. The scat (severe combined anemia and thrombocytopenia) mouse model is a model of IBMFS with a phenotype of pancytopenia cycling through crises and remission. Scat carries an autosomal recessive missense mutation in Rasa3 that results in RASA3 mislocalization and loss of function. RASA3 functions as a Ras-GTPase activating protein (GAP), and its loss of function in scat results in increased erythroid RAS activity and reactive oxygen species (ROS) and altered erythroid cell cycle progression, culminating in delayed terminal erythroid differentiation. Here we sought to further resolve the erythroid cell cycle defect in scat through ex vivo flow cytometric analyses. These studies revealed a specific G0/G1 accumulation in scat bone marrow (BM) polychromatophilic erythroblasts and scat BM Ter119

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