Characterization of miR-153 knockout and miR-153 transgenic mice: An initial analysis of its target genes in the brain and pancreas islets

Authors

• HX ZHANG
• JJ XIONG
• GN CARMONA
• A CHO
• T CAI
• AL NOTKINS

Abstract

Mir-153 has been found to play an important role in neuroendocrine secretion, behavior regulation, and tumor genesis. However, the underlying molecular mechanism of miR-153 remains to be determined. In the present study, we report the characterization of miR-153 knockout (KO) and transgenic (Tg) mouse models and phenotypical observation on islet-related insulin secretion and learning and memory behavior. Glucose tolerance tests showed impaired glucose tolerance in the miR-153 Tg mice, but not the KO mice, suggesting an impaired insulin section. Active avoidance test, where mice are trained to avoid a weak electric shock, showed that miR-153 KO mice performed significantly better by showing a greater number of active avoidance responses compared to their miR-153 Tg and wild type counterparts. To further understand the underlying molecular mechanisms of these alterations, we performed bioinformatics analyses and verified two previously undescribed target genes of miR-153 in pancreatic islet beta cells and brain hippocampus. Quantitative RT-PCR and Western blot analysis showed significant changes in expression of the islet-specific Ero1b gene and the hippocampus-specific NeuroD6 gene. Deletion of the Ero1lb or the NeuroD6 gene was previously found to develop a stable diabetic phenotype in mice or to affect neurogenesis in the brain. Taken together, we established for the first time the miR-153-/- and miR-153 Tg animal models and observed physiological and behavior alterations implicated in neuroendocrine secretion. Further studies of these two tissue-specific target genes of miR-153 in islet cells and hippocampus may shed new lights on how miR-153 is involved in neuroendocrine and neurogenesis-associated pathways.

Scientific Focus Area: Genetics and Genomics

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