In vivo analysis of Frat1 deficiency suggests compensatory activity of Frat3

The Frat1 gene was first identified as a proto-oncogene involved in progres sion of mouse T cell lymphomas. More recently, FRAT/GBP (GSK-3 beta Binding Protein) family members have been recognized as critical components of the Wnt signal transduction pathway. In an attempt to gain more insight into t he function of Frat1, we have generated Frat1-deficient mice in which most of the coding domain was replaced by a promoterless beta-galactosidase repo rter gene. While the pattern of LacZ expression in Frat1(lacZ)l + mice indi cated Frat1 to be Frat(lacZ) mice were apparently normal, healthy and ferti le. Tissues of expressed in various neural and epithelial tissues, homozygo us Frail homozygous Frat(lacZ) mice showed expression of a second mouse Fra t gene, designated Fmd. The Frat1 and Frat3 proteins are structurally and f unctionally very similar, since both Frat1 and Frat3 are capable of inducin g a secondary axis in Xenopus embryos. The overlapping expression patterns of Frat1 and Frat3 during murine embryogenesis suggest that the apparent di spensability of Frat1 for proper development may be due to the presence of a second mouse gene encoding a functional Frat protein. (C) 1999 Elsevier S cience Ireland Ltd. All rights reserved.