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  • Final Activity Report Summary - PAX7 TRANSGENICS (Conditional inactivation of Notch signalling during myogenesis by development and application of Pax7 specific transgenic mouse models)
FP6

PAX7 TRANSGENICS Report Summary

Project ID: 40382
Funded under: FP6-MOBILITY
Country: Portugal

Final Activity Report Summary - PAX7 TRANSGENICS (Conditional inactivation of Notch signalling during myogenesis by development and application of Pax7 specific transgenic mouse models)

This project has incorporated several project foci so as to maximize output in the 2 year fellowship period. This work can be grouped into two categories. Firstly, relating to Hox gene regulation of axial elongation and secondly relating to aspects of myogenesis and disorders associated with myogenesis.

With relation to Hox gene regulation of axial elongation, we have created transgenic mouse models to demonstrate that HoxC13 is able to impair axial elongation by impairment of Wnt and retinoic acid signaling without any observable impact on GDF signaling. FGF signaling is mildly impaired with overexpression of HoxC13 in mouse embryo presomitic mesoderm. This work is in review for Developmental Cell in a collaborative paper with Jacqueline Deschamps from the Hubrecht Institute in Holland, and a second manuscript is in preparation to publish additional data generated from this project.

Relating to myogenesis investigation, two main avenues of investigation have been and continue to be underway. Firstly, we have been generating transgenic models for Pax7-Cre, and Pax7-RTTA in order to specifically delete floxed genes downstream of Pax7. Secondly, we have generated a targeted ES cell line to specifically ablate GNE in Cre expressing cell lines. GNE is the gene that when mutated is responsible for Heterologous Inclusion Body Myopathy. We are currently breeding chimeric mice generated from these ES cells and will investigate the impact of tissue specific deletions on myogenesis. This work has been funded additionally by the Association for Research Myopathies.

Contact

Moises MALLO, (Principal Investigator)
Tel.: +351-214464624
Fax: +351 214407970
E-mail
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