Gfi1 P2A/P2A knock-in mouse model to study defects in hematopoiesis and inner ear development

The Snail/Gfi1 (SNAG) family of zinc finger proteins is a group of transcriptional repressors. Gfi1 is expressed in the hematopoietic and nervous system. Consequently, mutations of Gfi1 cause defects in hematopoiesis and inner ear development. In the Gfi1P2A/P2A mouse strain, a point mutation has been inserted in the SNAG domain that replaces a proline at amino acid position 2 by alanine (P2A). This completely abrogates the activity of Gfi1 as transcriptional repressor. Gfi1 and its paralogue Gfi1b have overlapping, however differential functions in hematopoiesis. Loss of Gfi1 in mice affects pre-T-cell differentiation, the development of neutrophil granulocytes and inner ear hair cells, whereas in contrast loss of Gfi1b impairs the development of erythroid cells and megacaryocytes. Therefore, Gfi1P2A/P2A mice can be used as a model to study and treat deafness as a consequence of defects of inner ear development as well as defects of hematopoiesis in immunological disorders.

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