PMID- 19661183
OWN - NLM
STAT- MEDLINE
DCOM- 20100203
LR  - 20191210
IS  - 1460-2083 (Electronic)
IS  - 0964-6906 (Linking)
VI  - 18
IP  - 22
DP  - 2009 Nov 15
TI  - Knock-down of PQBP1 impairs anxiety-related cognition in mouse.
PG  - 4239-54
LID - 10.1093/hmg/ddp378 [doi]
AB  - PQBP1 (polyglutamine tract-binding protein 1) is a causative gene for a 
      relatively frequent X-linked syndromic and non-syndromic mental retardation (MR). 
      To analyze behavioral abnormalities of these patients from molecular basis, we 
      developed a knock-down (KD) mouse model. The KD mice possess a transgene 
      expressing 498 bp double-strand RNA that is endogenously cleaved to siRNA 
      suppressing PQBP1 efficiently. After confirming that PQBP1 is selectively 
      suppressed to nearly 50% of the control mice, we performed behavioral analyses of 
      PQBP1-KD mice. The KD mice possessed normal ability in ordinary memory tests 
      including water-maze test, whereas they showed abnormal anxiety-related behavior 
      in light/dark exploration test and open-field test and showed obvious declines of 
      anxiety-related cognition in the repetitive elevated plus maze or novel object 
      recognition test. Correspondingly, we found c-fos upregulation and histone H3 
      acetylation after behavior tests were declined in neurons of amygdala, prefrontal 
      cortex and hippocampus. Furthermore, we found that 4-phenylbutyric acid, an HDAC 
      inhibitor, efficiently improved expression of these genes and rescued the 
      abnormal phenotypes in adult PQBP1-KD mice. These results suggested that PQBP1 
      dysfunction in regulating gene expression might underlie the abnormal behavior 
      and cognition of PQBP1-KD mice and that the recovery of expression of such PQBP1 
      target genes might improve the symptoms in adult patients.
FAU - Ito, Hikaru
AU  - Ito H
AD  - Department of Neuropathology, Medical Research Institute and 21st Century Center 
      of Excellence Program (COE) for Brain Integration and Its Disorders, Tokyo 
      Medical and Dental University, Tokyo, Japan.
FAU - Yoshimura, Natsue
AU  - Yoshimura N
FAU - Kurosawa, Masaru
AU  - Kurosawa M
FAU - Ishii, Shunsuke
AU  - Ishii S
FAU - Nukina, Nobuyuki
AU  - Nukina N
FAU - Okazawa, Hitoshi
AU  - Okazawa H
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20090806
PL  - England
TA  - Hum Mol Genet
JT  - Human molecular genetics
JID - 9208958
RN  - 0 (Carrier Proteins)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Nuclear Proteins)
RN  - 0 (Pqbp1 protein, mouse)
SB  - IM
MH  - Animals
MH  - Anxiety/*genetics/metabolism/*psychology
MH  - Carrier Proteins/*genetics/metabolism
MH  - *Cognition
MH  - DNA-Binding Proteins
MH  - Disease Models, Animal
MH  - Female
MH  - Gene Expression
MH  - Gene Knockdown Techniques
MH  - Humans
MH  - Male
MH  - Maze Learning
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Nuclear Proteins/*genetics/metabolism
EDAT- 2009/08/08 09:00
MHDA- 2010/02/04 06:00
CRDT- 2009/08/08 09:00
PHST- 2009/08/08 09:00 [entrez]
PHST- 2009/08/08 09:00 [pubmed]
PHST- 2010/02/04 06:00 [medline]
AID - ddp378 [pii]
AID - 10.1093/hmg/ddp378 [doi]
PST - ppublish
SO  - Hum Mol Genet. 2009 Nov 15;18(22):4239-54. doi: 10.1093/hmg/ddp378. Epub 2009 Aug 
      6.