Mitf and Tfe3, two members of the Mitf-Tfe family of bHLH-Zip transcription factors, have important but functionally redundant roles in osteoclast development

Eiríkur Steingrímsson, Lino Tessarollo, Bhavani Pathak, Ling Hou, Heinz Arnheiter, Neal G. Copeland, Nancy A. Jenkins

Rannsóknarafurð: Framlag til fræðitímaritsGreinritrýni

162 Tilvitnanir (Scopus)

Útdráttur

The Mitf-Tfe family of basic helix-loop-leucine zipper (bHLH- Zip) transcription factors encodes four family members: Mitf, Tfe3, Tfeb, and Tfec. In vitro, each protein in the family can bind DNA as a homo- or heterodimer with other family members. Mutational studies in mice have shown that Mitf is essential for melanocyte and eye development, whereas Tfeb is required for placental vascularization. Here, we uncover a role for Tfe3 in osteoclast development, a role that is functionally redundant with Mitf. Although osteoclasts seem normal in Mitf or Tfe3 null mice, the combined loss of the two genes results in severe osteopetrosis. We also show that Tfec mutant mice are phenotypically normal, and that the Tfec mutation does not alter the phenotype of Mitf, Tfeb, or Tfe3 mutant mice. Surprisingly, our studies failed to identify any phenotypic overlap between the different Mitf-Tfe mutations. These results suggest that heterodimeric interactions are not essential for Mitf-Tfe function in contrast to other bHLH-Zip families like Myc/Max/Mad, where heterodimeric interactions seem to be essential.

Upprunalegt tungumálEnska
Síður (frá-til)4477-4482
Síðufjöldi6
FræðitímaritProceedings of the National Academy of Sciences of the United States of America
Bindi99
Númer tölublaðs7
DOI
ÚtgáfustaðaÚtgefið - 2 apr. 2002

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