DeltaNp73 transcription factors modulate cell survival and tumor development.
The p73 locus encodes two types of transcription factors: full length pro-apoptotic isoforms (TAp73), and N-terminally truncated anti-apoptotic proteins (DeltaNp73). To study the function of DeltaNp73 in vivo, we generated mutant mice in which DeltaNp73 is inactivated, but TAp73 expression is intact. In addition, we knocked in the locus the Cre recombinase, and the enhanced green fluorescent protein (EGFP). Using this allele, we refined the expression of DeltaNp73 during brain development and emphasized the importance of the thalamic eminence, a transient source that contributes neurons to the telencephalon. We showed that DeltaNp73 inactivation increases apoptosis in neurons. We also investigated the role of DeltaNp73 in carcinogenesis by inducing tumors with methylcholanthrene in mutant and control mice, and found that mutant females, but not males, have decreased propensity to tumor development. Both effects on neuronal apoptosis and tumor development were milder than predicted from in vitro studies.
Ravni
Aurélia
A
Institute of Neuroscience, University of Louvain, Brussels, Belgium.
Tissir
Fadel
F
Goffinet
André M
AM
D000818:Animals; D017209:Apoptosis; D001921:Brain / Q000254:growth & development; D002470:Cell Survival; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D005260:Female; D055879:Gene Knock-In Techniques; D019426:Integrases / Q000235:genetics / Q000378:metabolism; D008297:Male; D008748:Methylcholanthrene / Q000633:toxicity; D051379:Mice; D018345:Mice, Knockout; D009369:Neoplasms / Q000139:chemically induced / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology
D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D020033:Protein Isoforms; C000606368:Trp73 protein, mouse; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins; D008748:Methylcholanthrene; C045073:Cre recombinase; D019426:Integrases