Modeling GATA2 deficiency in mice: the R396Q mutation disrupts normal hematopoiesis.

ABSTRACT: GATA2 deficiency is an autosomal dominant germline disorder of immune dysfunction and bone marrow failure with a high propensity for leukemic transformation. While sequencing studies have identified several secondary mutations thought to contribute to malignancy, the mechanisms of disease progression have been difficult to identify due to a lack of disease-specific experimental models. Here, we describe a murine model of one of the most common GATA2 mutations associated with leukemic progression in GATA2 deficiency, Gata2^R396Q/+. While mutant mice exhibit mild defects in peripheral blood, they display significant hematopoietic abnormalities in the bone marrow, including a reduction in hematopoietic stem cell (HSC) function and intrinsic biases toward specific stem cell subsets t

SUBMITTER: Hall T 

PROVIDER: S-EPMC11879863 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature