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Important Roles of Ring Finger Protein 112 in Embryonic Vascular Development and Brain Functions

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Abstract

Rnf112 is a member of the RING finger protein family. The expression of Rnf112 is abundant in the brain and is regulated during brain development. Our previous study has revealed that Rnf112 can promote neuronal differentiation by inhibiting the progression of the cell cycle in cell models. In this study, we further revealed the important functions of Rnf112 in embryo development and in adult brain. Our data showed that most of the Rnf112 −/− embryos exhibited blood vascular defects and died in utero. Upon further investigation, we found that the survival rate of homozygous Rnf112 knockout mice in 129/sv and C57BL/6 mixed genetic background was increased. The survived newborns of Rnf112 −/− mice manifested growth retardation as indicated by smaller size and a reduced weight. Although the overall organization of the brain did not appear to be severely affected in Rnf112 −/− mice, using in vivo 3D MRI imaging, we found that when compared to wild-type littermates, brains of Rnf112 −/− mice were smaller. In addition, Rnf112 −/− mice displayed impairment of brain functions including motor balance, and spatial learning and memory. Our results provide important aspects for the study of Rnf112 gene functions.

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Acknowledgments

This work was supported by the National Science Council, Republic of China (NSC 102-2320-B-038-024), Ministry of Science and Technology, Republic of China (MOST 103-2320-B-038-034, MOST 103-2320-B-197-002), and Taipei Medical University (TMU101-AE3-Y24). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. We thank the technical services provided by the “Transgenic Mouse Model Core Facility of the National Core Facility Program for Biotechnology, National Science Council” and the “Gene Knockout Mouse Core Laboratory of National Taiwan University Center of Genomic Medicine.” We also thank the technical supports from the Taiwan Mouse Clinic (MOST 104-2325-B-001-011) which is funded by the National Research Program for Biopharmaceuticals (NRPB) at the Ministry of Science and Technology (MOST) of Taiwan. We thank Ms. Christine Chin-jung Hsieh for the English language editing of the manuscript.

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Authors and Affiliations

  1. Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan

    Jen-Hui Tsou, Ping-Chieh Pao & Wen-Chang Chang

  2. Department of Biotechnology and Animal Science, College of Bioresources, National Ilan University, Ilan, Taiwan

    Ying-Chen Yang

  3. Department and Institute of Physiology, School of Medicine, National Yang-Ming University, Taipei, Taiwan

    Hui-Ching Lin

  4. Brain Research Center, National Yang-Ming University, Taipei, Taiwan

    Hui-Ching Lin

  5. National Research Institute of Chinese Medicine, Taipei, Taiwan

    Nai-Kuei Huang

  6. Ph.D. Program for Neural Regenerative Medicine, College of Medical Science and Technology, Taipei Medical University, Taipei, 11031, Taiwan

    Nai-Kuei Huang, Chu-Jen Kuo, Jiann-Her Lin & Yi-Chao Lee

  7. Department of Pharmacology, College of Medicine, National Cheng Kung University, Tainan, Taiwan

    Shih-Ting Lin & Kuei-Sen Hsu

  8. Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan

    Che-Ming Yeh

  9. Graduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan

    Kuen-Haur Lee

  10. Department of Radiology, Shin Kong Wu Ho-Su Memorial Hospital, School of Medicine, Fu Jen Catholic University, Taipei, Taiwan

    Chu-Jen Kuo

  11. Department of Medical Research and Education, Taipei Veterans General Hospital, Taipei, Taiwan

    De-Ming Yang

  12. Institute of Biophotonics, School of Medical Technology and Engineering, National Yang-Ming University, Taipei, Taiwan

    De-Ming Yang

  13. Center for Neurotrauma and Neuroregeneration, Taipei Medical University, Taipei, Taiwan

    Yi-Chao Lee

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  1. Jen-Hui Tsou
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  14. Yi-Chao Lee
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Corresponding author

Correspondence to Yi-Chao Lee.

Additional information

Jen-Hui Tsou and Ying-Chen Yang contributed equally to this work.

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Supplemental Fig. 1

MRI images of mouse brain. Axial (a) and coronal (b–d) views of MRI. Data was obtained from the 5 wild type (Rnf112 +/+) and 4 homozygous Rnf112-knockout (Rnf112 −/−) mice (PDF 16652 kb)

Supplemental Fig. 2

Expression of Rnf112 in umbilical cord. Western blot analysis of Rnf112 and β-actin expressions in the indicated tissues (PDF 838 kb)

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Tsou, JH., Yang, YC., Pao, PC. et al. Important Roles of Ring Finger Protein 112 in Embryonic Vascular Development and Brain Functions. Mol Neurobiol 54, 2286–2300 (2017). https://doi.org/10.1007/s12035-016-9812-7

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  • DOI: https://doi.org/10.1007/s12035-016-9812-7

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