Gfi1 P2A/P2A knock-in mouse model
A 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.
In vivo model with significant defects of inner ear development and hematopoiesis:
- study deafness
- develop new approaches to treat deafness
- study immunological disorders
On behalf of the University of Duisburg-Essen, PROvendis offers access to the mouse model under a Material License Agreement.
Publikationen & Verweise
Fiolka, K., et al. (2006) Gfi1 and Gfi1b act equivalently in haematopoiesis, but have distinct, non-overlapping functions in inner ear development. EMBO Reports 7(3): 326-33.
Möröy, T. (2005) The zinc finger transcription factor Growth factor independence 1 (Gfi1). Int. J. Biochem. Cell Biol. 37: 541-6.
Wallis, D., et al. (2003) The zinc finger transcription factor Gfi1, implicated in lymphomagenesis, is required for inner ear hair cell differentiation and survival. Development. 130: 221-32.
Saleque, S. et al. (2002) The zinc-finger proto-oncogene Gfi-1b is essential for development of the erythroid and megakaryocytic lineages. Genes Dev. 16: 301-6.
StichworteSNAG, Zinkfinger-Proteine, Epxressionsrepressoren, Entwicklung des Innenohrs, Taubheit, Hämatopoese SNAG, zinc finger proteins, expression repressors, inner ear development, deafness, hematopoiesis