Functional Validation of Candidate Genes for ARM and EEC in Mice
The mouse is an excellent model for analyzing the genetic basis of human disease in vivo. In this subproject mouse models are established in order to examine and validate genes, identified as candidates for causing Anorectal Malformations or Bladder Exstrophy Epispadias Complex in human patients, in the mouse. Candidate genes identified in human patients are analysed for their expression patterns in mouse embryos in order to allow prioritization for further analyses, followed by genetic examination of patient cohorts and functional analysis in the mouse. Genes with high probability of functional involvement in human phenotypes are selected for functional analysis using conditional knock-out, knock-down and/or transgenic approaches. This will unequivocally identify the gene(s) causing Anorectal Malformations or Bladder Exstrophy Epispadias Complex.
In addition a previously described model for ano-recto-caudal syndrome in the mouse is established and analysed by expression profiling and marker gene analyses. The goal of the functional analyses is to understand urogenital and hindgut development in more detail and to integrate these processes into regulatory networks of trunk development.