PMID- 24272708
OWN - NLM
STAT- MEDLINE
DCOM- 20140716
LR  - 20191210
IS  - 1098-1136 (Electronic)
IS  - 0894-1491 (Linking)
VI  - 62
IP  - 1
DP  - 2014 Jan
TI  - Nbn gene inactivation in the CNS of mouse inhibits the myelinating ability of the 
      mature cortical oligodendrocytes.
PG  - 133-44
LID - 10.1002/glia.22593 [doi]
AB  - Nijmegen Breakage Syndrome (NBS) is a recessive genetic disorder characterized by 
      immunodeficiency, elevated sensitivity to ionizing radiation, chromosomal 
      instability, microcephaly, and high predisposition to malignancies. Since the 
      underlying molecular mechanisms of the NBS microcephaly are still obscure, thus 
      our group previously inactivated the Nbn gene in the central nervous system (CNS) 
      of mice by nestin-Cre targeting gene system, and generated Nbn(CNS-del) mice. 
      Interestingly, the newborn Nbn(CNS-del) mice exhibit obvious microcephaly, which 
      is accompanied by severe ataxia and balance deficiency. In this study presented 
      here, we report that Nbn-deficiency induces the enhanced apoptosis of the mature 
      oligodendrocytes at postnatal day 7, which further affects the myelination of the 
      nerve fibers of cerebrum and corpus callosum.The distinct regulatory roles of 
      Ataxia telangiectasia mutated (ATM) signaling and protein kinase B(Akt)/the 
      mammalian target of Rapamycin (AKT/mTOR) signaling are responsible for the 
      enhanced apoptosis of the Nbn-deficient oligodendrocytes. In addition, a series 
      of transcriptional factors including histonedeacetylase (HDAC), zinc finger 
      protein 191 (ZFP-191) and myelin sheath regulatory factor (MRF) play distinct 
      roles in regulating the myelination of the Nbn-deficient oligodendrocytes. Based 
      on these results, it concludes that ATM-Chk2-P53-P21 signaling pathway and the 
      AKT/mTOR signaling pathway are both responsible for the enhanced apoptosis of the 
      Nbn-deficient oligodendrocytes. HDAC, ZFP-191, and MRF are also involved in the 
      pathogenesis of the hypomyelination of the Nbn-deficient oligodendrocytes.
CI  - Copyright (c) 2013 Wiley Periodicals, Inc.
FAU - Liu, Bo
AU  - Liu B
AD  - Department of Pathology, Center for Experimental Animal Research, Institute of 
      Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union 
      Medical College, Beijing, China.
FAU - Chen, Xin
AU  - Chen X
FAU - Wang, Zhao-Qi
AU  - Wang ZQ
FAU - Tong, Wei-Min
AU  - Tong WM
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Glia
JT  - Glia
JID - 8806785
RN  - 0 (Cell Cycle Proteins)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Myelin Proteins)
RN  - 0 (Nestin)
RN  - 0 (Nijmegen breakage syndrome 1 protein, mouse)
RN  - 0 (Nuclear Proteins)
SB  - IM
MH  - Animals
MH  - Animals, Newborn
MH  - Apoptosis/physiology
MH  - Cell Cycle Proteins/genetics/*metabolism
MH  - Cells, Cultured
MH  - Central Nervous System/*metabolism
MH  - Cerebral Cortex/*cytology
MH  - Corpus Callosum/metabolism
MH  - DNA-Binding Proteins
MH  - Down-Regulation/genetics
MH  - Mice
MH  - Mice, Transgenic
MH  - Myelin Proteins/*metabolism
MH  - Myelin Sheath/metabolism/ultrastructure
MH  - Nestin/genetics
MH  - Nuclear Proteins/genetics/*metabolism
MH  - Oligodendroglia/metabolism/*physiology/ultrastructure
MH  - Signal Transduction/genetics/*physiology
OTO - NOTNLM
OT  - DNA damage
OT  - Nbn protein
OT  - mature oligodendrocytes
OT  - myelination
OT  - signaling pathways
EDAT- 2013/11/26 06:00
MHDA- 2014/07/17 06:00
CRDT- 2013/11/26 06:00
PHST- 2013/08/13 00:00 [received]
PHST- 2013/10/07 00:00 [revised]
PHST- 2013/10/17 00:00 [accepted]
PHST- 2013/11/26 06:00 [entrez]
PHST- 2013/11/26 06:00 [pubmed]
PHST- 2014/07/17 06:00 [medline]
AID - 10.1002/glia.22593 [doi]
PST - ppublish
SO  - Glia. 2014 Jan;62(1):133-44. doi: 10.1002/glia.22593.