Transcription profiling of mice hearts comparing microRNA-22 KO to wildtype

To explore the role of miR-22 in the heart, we generated miR-22 null and transgenic mice. Absence of miR-22 results in partial embryonic lethality arising from cardiac malformations. miR-22-null mice that survived until adulthood showed normal cardiac structure and function at baseline but were sensitized to cardiac dysfunction and dilation following pressure overload stimulation. Absence of miR-22 prevented the induction of beta-myosin heavy chain (Myh7) and miR-208b expression following pathologic stress. miR-22 null animals were also compromised in cardiac expression of Myh7b and miR-499. We found that miR-22 directly regulates two transcriptional antagonists, purine rich element binding protein B (PURB), a repressor, and serum response factor (SRF), an activator, in the heart. Through these gain- and loss-of-function experiments in mice, we suggest that a primary function of miR-22 is to fine tune the relative expression and activity of these two transcriptional antagonists to influence contractile gene expression, function, growth and adaptation of the heart to stress.