TRPC4 deletion elicits behavioral defects in sociability by dysregulating expression of microRNA-138-2
Jee Young Seo,
Hye-Ryeong Jo,
Seung Hoon Lee,
Do Gyeong Kim,
Huiju Lee,
Ye Lim Kim,
Young In Choi,
Sung Jun Jung,
Hyeon Son
Affiliations
Jee Young Seo
Graduate School of Biomedical Science and Engineering, Hanyang Biomedical Research Institute, Hanyang University, 222 Wangsimni-ro, Seongdong-gu, Seoul, Korea
Hye-Ryeong Jo
Hanyang University Hospital for Rheumatic Diseases, 222 Wangsimni-ro, Seongdong-gu, Seoul, Korea
Seung Hoon Lee
Hanyang University Hospital for Rheumatic Diseases, 222 Wangsimni-ro, Seongdong-gu, Seoul, Korea
Do Gyeong Kim
Graduate School of Biomedical Science and Engineering, Hanyang Biomedical Research Institute, Hanyang University, 222 Wangsimni-ro, Seongdong-gu, Seoul, Korea
Huiju Lee
Graduate School of Biomedical Science and Engineering, Hanyang Biomedical Research Institute, Hanyang University, 222 Wangsimni-ro, Seongdong-gu, Seoul, Korea
Ye Lim Kim
Graduate School of Biomedical Science and Engineering, Hanyang Biomedical Research Institute, Hanyang University, 222 Wangsimni-ro, Seongdong-gu, Seoul, Korea
Young In Choi
Department of Physiology, College of Medicine, Hanyang University, 222 Wangsimni-ro, Seongdong-gu, Seoul, Korea
Sung Jun Jung
Graduate School of Biomedical Science and Engineering, Hanyang Biomedical Research Institute, Hanyang University, 222 Wangsimni-ro, Seongdong-gu, Seoul, Korea; Department of Physiology, College of Medicine, Hanyang University, 222 Wangsimni-ro, Seongdong-gu, Seoul, Korea; Corresponding author
Hyeon Son
Graduate School of Biomedical Science and Engineering, Hanyang Biomedical Research Institute, Hanyang University, 222 Wangsimni-ro, Seongdong-gu, Seoul, Korea; Department of Biochemistry and Molecular Biology, College of Medicine, Hanyang University, 222 Wangsimni-ro, Seongdong-gu, Seoul, Korea; Corresponding author
Summary: To investigate whether the defects in transient receptor potential canonical 4 (TRPC4), which is strongly expressed in the hippocampus, are implicated in ASD, we examined the social behaviors of mice in which Trpc4 was deleted (Trpc4−/−). Trpc4−/− mice displayed the core symptoms of ASD, namely, social disability and repetitive behaviors. In microarray analysis of the hippocampus, microRNA (miR)-138-2, the precursor of miR-138, was upregulated in Trpc4−/− mice. We also found that binding of Matrin3 (MATR3), a selective miR-138-2 binding nuclear protein, to miR-138-2 was prominently enhanced, resulting in the downregulation of miR-138 in Trpc4−/− mice. Some parameters of the social defects and repetitive behaviors in the Trpc4−/− mice were rescued by increased miR-138 levels following miR-138-2 infusion in the hippocampus. Together, these results suggest that Trpc4 regulates some signaling components that oppose the development of social behavioral deficits through miR-138 and provide a potential therapeutic strategy for ASD.
