Unknown

Dataset Information

0

Targeted disruption of Tgif, the mouse ortholog of a human holoprosencephaly gene, does not result in holoprosencephaly in mice.


ABSTRACT: 5'-TG-3'-interacting factor or transforming growth factor beta (TGF-beta)-induced factor (TGIF) belongs to a family of evolutionarily conserved proteins that are characterized by an atypical three-amino-acid loop extension homeodomain. In vitro studies have implicated TGIF as a transcriptional repressor and corepressor in retinoid and TGF-beta signaling pathways that regulate several important biological processes. Heterozygous nonsense and missense mutations of the human TGIF gene have been associated with holoprosencephaly, the most common congenital malformation of the forebrain. In mice, Tgif mRNA is expressed ubiquitously in the ventricular neuroepithelium at embryonic day 10.5 (E10.5) but displays a medial to lateral gradient in the developing cerebral cortex at E12.5. The expression quickly declines by E14.5. The spatiotemporal expression profile of Tgif is consistent with its involvement in midline forebrain development. To better understand the function of Tgif in forebrain patterning and proliferation in vivo, we generated mice lacking Tgif by targeted deletion of exons 2 and 3, which encode 98% of the amino acids. Tgif(-)(/)(-) mice had no detectable Tgif protein by Western blotting. Surprisingly, however, these mice were viable and fertile. In addition, there were no discernible derangements in any of the major organ systems, including the forebrain. Overall our results point to a possible functional redundancy of Tgif, potentially provided by the closely related Tgif2.

SUBMITTER: Shen J 

PROVIDER: S-EPMC1084278 | biostudies-literature | 2005 May

REPOSITORIES: biostudies-literature

altmetric image

Publications

Targeted disruption of Tgif, the mouse ortholog of a human holoprosencephaly gene, does not result in holoprosencephaly in mice.

Shen Jun J   Walsh Christopher A CA  

Molecular and cellular biology 20050501 9


5'-TG-3'-interacting factor or transforming growth factor beta (TGF-beta)-induced factor (TGIF) belongs to a family of evolutionarily conserved proteins that are characterized by an atypical three-amino-acid loop extension homeodomain. In vitro studies have implicated TGIF as a transcriptional repressor and corepressor in retinoid and TGF-beta signaling pathways that regulate several important biological processes. Heterozygous nonsense and missense mutations of the human TGIF gene have been ass  ...[more]

Similar Datasets

| S-EPMC3214944 | biostudies-literature
| S-EPMC1820763 | biostudies-literature
| S-EPMC3285584 | biostudies-literature
| S-EPMC99560 | biostudies-literature
| S-EPMC2529283 | biostudies-literature
| S-EPMC115062 | biostudies-literature
| S-EPMC2987413 | biostudies-literature
| S-EPMC1592760 | biostudies-literature
| S-EPMC3309119 | biostudies-literature
| S-EPMC6365593 | biostudies-literature