Pax3:Fkhr Interferes with Embryonic Pax3 and Pax7 Function: Implications for Alveolar Rhabdomyosarcoma Cell of Origin

Overview

Journal Genes Dev

Specialty Molecular Biology

Date 2004 Nov 3

PMID 15520281

Citations 133

Authors

Charles Keller

Mark S Hansen

Cheryl M Coffin

Mario R Capecchi

Affiliations

Soon will be listed here.

Abstract

To investigate the role of the translocation-associated gene Pax3:Fkhr in alveolar rhabdomyosarcomas, we generated a Cre-mediated conditional knock-in of Pax3:Fkhr into the mouse Pax3 locus. Exploring embryonic tumor cell origins, we replaced a Pax3 allele with Pax3:Fkhr throughout its expression domain, causing dominant-negative effects on Pax3 and paradoxical activation of the Pax3 target gene, c-Met. Ectopic neuroprogenitor cell proliferation also occurs. In contrast, activation later in embryogenesis in cells that express Pax7 results in viable animals with a postnatal growth defect and a moderately decreased Pax7+ muscle satellite cell pool, phenocopying Pax7 deficiency but remarkably not leading to tumors.

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