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

Jen-Hui Tsou; Ying-Chen Yang; Ping-Chieh Pao; Hui-Ching Lin; Nai-Kuei Huang; Shih-Ting Lin; Kuei-Sen Hsu; Che-Ming Yeh; Kuen-Haur Lee; Chu-Jen Kuo; De-Ming Yang; Jiann-Her Lin; Wen-Chang Chang; Yi-Chao Lee

doi:10.1007/s12035-016-9812-7

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

Mol Neurobiol. 2017 Apr;54(3):2286-2300. doi: 10.1007/s12035-016-9812-7. Epub 2016 Mar 7.

Authors

Jen-Hui Tsou¹, Ying-Chen Yang², Ping-Chieh Pao¹, Hui-Ching Lin^{3

4}, Nai-Kuei Huang^{5

6}, Shih-Ting Lin⁷, Kuei-Sen Hsu⁷, Che-Ming Yeh⁸, Kuen-Haur Lee⁹, Chu-Jen Kuo^{6

10}, De-Ming Yang^{11

12}, Jiann-Her Lin⁶, Wen-Chang Chang¹, Yi-Chao Lee^{13

14}

Affiliations

¹ Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan.
² Department of Biotechnology and Animal Science, College of Bioresources, National Ilan University, Ilan, Taiwan.
³ Department and Institute of Physiology, School of Medicine, National Yang-Ming University, Taipei, Taiwan.
⁴ Brain Research Center, National Yang-Ming University, Taipei, Taiwan.
⁵ National Research Institute of Chinese Medicine, Taipei, Taiwan.
⁶ Ph.D. Program for Neural Regenerative Medicine, College of Medical Science and Technology, Taipei Medical University, Taipei, 11031, Taiwan.
⁷ Department of Pharmacology, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
⁸ Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
⁹ Graduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan.
¹⁰ Department of Radiology, Shin Kong Wu Ho-Su Memorial Hospital, School of Medicine, Fu Jen Catholic University, Taipei, Taiwan.
¹¹ Department of Medical Research and Education, Taipei Veterans General Hospital, Taipei, Taiwan.
¹² Institute of Biophotonics, School of Medical Technology and Engineering, National Yang-Ming University, Taipei, Taiwan.
¹³ Ph.D. Program for Neural Regenerative Medicine, College of Medical Science and Technology, Taipei Medical University, Taipei, 11031, Taiwan. yclee@tmu.edu.tw.
¹⁴ Center for Neurotrauma and Neuroregeneration, Taipei Medical University, Taipei, Taiwan. yclee@tmu.edu.tw.

PMID: 26951452
DOI: 10.1007/s12035-016-9812-7

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.

Keywords: Brain finger protein; Growth retardation; Memory impairment; Rnf112; Znf179.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Behavior, Animal / physiology*
Brain / blood supply*
Brain / embryology*
DNA-Binding Proteins / genetics
DNA-Binding Proteins / metabolism*
Imaging, Three-Dimensional / methods
Learning / physiology
Memory / physiology
Mice
Mice, Inbred C57BL
Mice, Knockout

Substances

DNA-Binding Proteins
ZNF179 protein, mouse