biostudies-arrayexpressIrina BochkisMus musculushttps://www.ebi.ac.uk/biostudies/studies/E-MEXP-1040An experiment was performed to analyze global expression changes in the testis of Foxa3 knockout mouse.biostudies-arrayexpressNucleic Acid Extraction - Total RNA was extracted using two rounds of Phenol extractionMIAME ScoreRaw DataOrganizationAssays and DataMAGE-TAB FilesArray DesignsData Transformation - The data was normalized using the GeneChip Robust Multi-Array Analysis (GCRMA) algorithm, implemented in an R package (http://www.bioconductor.org/repository/devel/vignette/gcrma.pdf). Fold-changes were calculated as the ratio of the geometric mean between wild type and Foxa3-/- intensities. Statistical analysis of the microarray data was completed using the significance of microarrays (SAM) package with a false discovery rate (FDR) of 10% and fold change cutoff of absolute value of 2.0. Annotation for each ‘spot’ was downloaded from the Affymetrix web site.MetabolomicsUnknownTranscriptomicsGenomicsProteomicsFoxa1, 2 and 3 (formerly HNF-3alpha, -beta and -gamma) constitute a sub-family of winged helix transcription factors with multiple roles in mammalian organ development. While all three Foxa mRNAs are present in endoderm derivatives including liver and pancreas, only Foxa3 is expressed in the testis. Here we demonstrate by genetic lineage tracing that Foxa3 is expressed in postmeiotic germ and interstitial Leydig cells. The germinal epithelium of Foxa3-deficient testes is characterized by a loss of germ cells secondary to an increase in germ cell apoptosis that ultimately leads to a Sertoli cell-only syndrome. Remarkably, not only the Foxa3(-/-) mice but also Foxa3(+/-) mice exhibited loss of germ cells. This cellular phenotype caused significantly reduced fertility and testis weight of both Foxa3(-/-) and Foxa3(+/-) mice. Using microarray analysis, we found a dramatic downregulation of the zinc finger protein 93 and the testicular tumor-associated paraneoplastic Ma antigen (PNMA) and increased expression of a number of genes including zinc finger protein 94 and several kallikrein 1-related peptidases which could account for at least part of the observed phenotype. In summary, we have identified Foxa3 as a transcriptional regulator with a dominant phenotype in germ cell maintenance and suggest FOXA3 as a potential candidate gene for subfertility in man.transcription profiling by arrayMus musculusImpaired male fertility and atrophy of seminiferous tubules caused by haploinsufficiency for Foxa3Irina BochkisRudiger Behr; Sara Sackett; Irina Bochkis; Phillip Le; Klaus KaestnerfalseTranscription profiling of testis from Foxa3 knock-out miceAn experiment was performed to analyze global expression changes in the testis of Foxa3 knockout mouse.2007-03-16T00:00:00Z2022-03-07T04:53:57.697Z2022-03-07T04:53:57.697ZE-MEXP-104017488644EFO_000276810.1016/j.ydbio.2007.03.525