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Deficiency of antisense lncRNA Gm48853 resulted in embryonic lethality and impaired placental development in mice

Objective: Long noncoding RNAs (lncRNAs) play important roles in embryonic development and in various diseases. Gm48853 is a predicted natural antisense lncRNA gene of unknown function. The present study aimed to investigate its expression and function. Methods: Quantitative reverse transcription-polymerase chain reaction and sequencing were used to detect the expression of Gm48853 antisense lncRNA. Hematoxylin and eosin staining and pathological analysis were applied to evaluate the effects of Gm48853 mutations on embryonic/placental development. 5-Ethynyl-2'-deoxyuridine (EdU) and terminal deoxynucleotidyl transferase deoxy-UTP-nick-end labeling assays were used to analyze the status of cell proliferation and apoptosis in Gm48853- deficient embryos and placentas. Results: PiggyBac (PB) transposon insertion into the intron of Gm48853 resulted in a significant decrease in Gm48853 expression and embryonic lethality at midgestation. Homozygous Gm48853 mutations led to severe growth retardation of embryos and impaired the morphogenesis of the placental labyrinth. In addition, cell proliferation was dramatically decreased in Gm48853PB/PB embryos and placentas, and apoptosis was radically increased in the mutant embryos but not in the mutant placentas. Conclusion: Antisense lncRNA Gm48853 may regulate embryonic/placental development by enhancing cell proliferation and/or inhibiting apoptosis.