Increased Expression of Angiogenic Genes in the Brains of Mouse Meg3-null Embryos

MEG3 (Maternally Expressed Gene 3) is a non-coding RNA that is highly expressed in the normal human brain and pituitary. Expression of MEG3 is lost in gonadotroph-derived clinically non-functioning pituitary adenomas. Meg3 knock-out mice were generated to identify targets and potential functions of this gene in embryonic development and tumorigenesis. Gene expression profiles were compared in the brains of Meg3-null embryos and wild-type litter-mate controls using microarray analysis. Microarray data were analyzed with GeneSifter which uses Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways and Gene Ontology (GO) classifications to identify signaling cascades and functional categories of interest within the data set. Differences were found in signaling pathways and ontologies related to angiogenesis between wild-type and knock-out embryos. Quantitative RT-PCR and histological staining showed increased expression of some VEGF pathway genes and increased cortical microvessel density in the knock-out embryos. These results are consistent with reported increases in VEGF signaling observed in human clinically non-functioning pituitary adenomas. In conclusion, Meg3 may play an important role in control of vascularization in the brain and may function as a tumor suppressor by preventing angiogenesis. Brains from 7 Meg3 knock-out and 6 wild-type E18.5 embryos from 5 litters. genotype: wild-type: 219_16 WT, 219_17 WT, 238_4 WT, 250_2 WT, 250_4 WT, 262_2 WT genotype: Meg3 knock-out: 148_15 KO, 219_12 KO, 238_1 KO, 238_5 KO, 250_1 KO, 250_3 KO, 262_1 KO biological replicate: 219_16 WT, 219_17 WT, 238_4 WT, 250_2 WT, 250_4 WT, 262_2 WT biological replicate: 148_15 KO, 219_12 KO, 238_1 KO, 238_5 KO, 250_1 KO, 250_3 KO, 262_1 KO