Abstract
Growth factor signaling leads to the induction or repression of immediate early genes, but how these genes act collectively as effectors of downstream processes remains unresolved. We have used gene trap–coupled microarray analysis to identify and mutate multiple platelet-derived growth factor (PDGF) intermediate early genes in mice. Mutations in these genes lead to a high frequency of phenotypes that affect the same cell types and processes as those controlled by the PDGF pathway. We conclude that these genes form a network that controls specific processes downstream of PDGF signaling.
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Acknowledgements
We thank P. Corrin and M. Grenley for excellent technical assistance; B. Hoplight for assistance with statistical analysis and our laboratory colleagues S. Parkhurst and M. Van Gilst for critical reading of the manuscript. The Sox10 probe was a gift of M. Wegner (Universität Erlangen). J.S. and C.S.R. were the recipients of postdoctoral fellowships from the US National Institute of General Medical Sciences (GM071158) and from the Leukemia and Lymphoma Society, respectively, and both were supported by a Chromosome and Metabolism Training Grant (CA09657). This work was supported by grant HD24875 from the National Institute of Child Health and Human Development to P.S.
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J.S. and P.S. conceived and designed the experiments, P.S. generated chimeras and determined viability of mutant strains, C.S.R. focused on Sgpl1−/− mice, J.S. performed characterization of all the strains and analyzed the data and J.S. and P.S. wrote the paper.
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Supplementary information
Supplementary Fig. 1
Identification and verification of the insertion sites of the gene trap construct. (PDF 319 kb)
Supplementary Fig. 2
PDGF target genes are expressed in PDGF-dependent tissues. (PDF 305 kb)
Supplementary Fig. 3
Expression of PDGF target genes is altered in PDGFRβ−/− embryos. (PDF 223 kb)
Supplementary Table 1
Gene identification and insertion site. (PDF 92 kb)
Supplementary Table 2
Viability is reduced in mice with mutations in PDGF target genes. (PDF 95 kb)
Supplementary Table 3
Penetrance of skeletal defects in affected bones. (PDF 53 kb)
Supplementary Table 4
Primers used for genotyping mutant mice, for RT-PCR and for semiquantitative PCR. (PDF 60 kb)
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Schmahl, J., Raymond, C. & Soriano, P. PDGF signaling specificity is mediated through multiple immediate early genes. Nat Genet 39, 52–60 (2007). https://doi.org/10.1038/ng1922
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DOI: https://doi.org/10.1038/ng1922
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