Dominant negative Gfi1b mutations cause moderate thrombocytopenia and an impaired stress thrombopoiesis associated with mild erythropoietic abnormalities in mice.

ABSTRACT: GFI1B-related thrombocytopenia (GFI1B-RT) is a rare bleeding disorder mainly caused by the presence of truncated GFI1B proteins with dominant-negative properties. The disease is characterized by low platelet counts, the presence of abnormal platelets, a megakaryocytic expansion and mild erythroid defects. However, no animal models faithfully reproducing the GFI1B-RT phenotype observed in patients exist. We had previously generated mice with floxed Gfi1b alleles that can be eliminated by Cre recombinase, but those animals developed a much more severe phenotype than GFI1B-RT patients and were of limited interest in assessing the disease. Using CRISPR/Cas9 technology, we have now established three independent mouse lines that carry mutated Gfi1b alleles producing proteins lacking DNA binding

SUBMITTER: Beauchemin H 

PROVIDER: S-EPMC7556681 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature