MIA overexpression

In experiments using tissue recombinants and mesenchyme-free culture, we have demonstrated that the entire embryonic respiratory tract epithelium, from the trachea to the distal lung tips, exhibits substantial plasticity in its eventual phenotype that is dependent on the inductive cues it receives from its associated mesenchyme. This observation led us to speculate that the differences between embryonic trachea and lung are defined by limited subset of genes, and that the molecular comparison of these two tissues might provide new information on genes that are important for both lung and trachea development. Microarray experiments designed to identify genes differentially expressed in the E11.5 lung and trachea showed that melanoma inhibitory activity (Mia1) was expressed only in the lung. Mia1 was abundantly expressed during early lung development, but was virtually absent by the end of gestation. Bitransgenic mice expressing MIA under the control of the SFTPC promoter after E16.5, the age when Mia1 is normally silenced, died from respiratory failure at birth with morphologically immature lungs associated with reduced levels of saturated phosphatidylcholine and mature SP-B. Microarray analysis showed significant reductions expression of Sftpa, Sftpb, Abca3, Aqp5, Lzp-s, Scd2, and Aytl2 in lungs misexpressing MIA. Keywords: genotype comparison To identify genes differentially expressed in the embryonic lung and trachea, we used microarray analysis to compare RNA from day E11.5 mouse lung and trachea. To assess the effect of misexpressing MIA on overall lung gene expression, we analyzed RNA from day E18.5 lungs of bitransgenic and control littermates by microarray (Affymetrix MOE430 chip).