Gfi1 is a transcriptional repressor being expressed in the hematopoietic and nervous system. Loss of function leads to severe defects in hematopoiesis and inner ear development. Gfi1 is highly similar to its paralogue Gfi1b with almost identical sequences in their respective protein domains.Ut
A knock-in mouse model was created in which the Gfi1 coding region was replaced by Gfi1b.
The Gfi11b/1b-mice did not exhibit significant defects in the hematopoietic system as previously described for Gfi1-/--mice, suggesting that Gfi1b is able to rescue the loss of Gfi1-function.
Interestingly, however, the Gfi11b/1b-mice showed significant defects in inner ear development, i.e. hair cell formation, leading to hearing loss.
These results point to some interesting mechanisms on the molecular level for the differentiation and maintenance of hearing.
This makes the Gfi11b/1b-model a valuable tool for the development of novel approaches for treating hearing loss.
On behalf of the University of Duisburg-Essen, PROvendis offers access to the mouse model under a Material License Agreement.
A matching mouse model of a Gfi1 point mutation, Gfi1P2A/P2A is available with Ref. No. 3947.
Fiolka et al. (2006): Gfi1 and Gfi1b act equivalently in haematopoiesis, but have distinct, non-overlapping functions in inner ear development. EMBO Reports, 7(3): 326-333.
Möröy (2005): The zinc finger transcription factor Growth factor independence 1 (Gfi1). Int J Biochem Cell Biol. 37: 541-546.
Wallis et al. (2003): The zinc finger transcription factor Gfi1, implicated in lymphomagenesis, is required for inner ear hair cell differentiation and survival development. 130: 221-232.
Saleque et al. (2002): The zinc-finger proto-oncogene Gfi-1b is essential for development of the erythroid and megakaryocytic lineages. Genes Dev. 16: 301-306.