Alternative splicing Hltf: intron retention-dependent activation of immune tolerance at the feto-maternal interface (RNA-Seq)

Purpose: we tested the hypothesis that Hltf deletion in placenta either caused or exacerbated neonatal hypoglycemia via Hif-1α regulation of nutrient transporters. Methods: Individual samples [1 term placenta/sample x 5 biological replicates for test and control littermate female mice = 10 total samples] were flash frozen and sent to Otogenetics Corp. (Norcross, GA) for RNA-seq assays. Paired-end 100 nucleotide reads were aligned to genomic assembly mm10 and analyzed using the platform provided by DNAnexus, Inc. (Mountain View, CA). Results: There was no measureable evidence of uteroplacental dysfunction or fetal compromise. Conclusion: Our study is the first to show only the truncated Hltf isoform is expressed in E18.5 term placenta, and we identified a functional link between alternative splicing of Hltf and immunosuppression at the feto-maternal interface. Placental mRNA profiles of E18.5 term placenta from five wild type control and five Hltf null mouse samples were generated by deep sequencing by Illumina HiSeq2000/2500.