PMID- 19347959
OWN - NLM
STAT- MEDLINE
DCOM- 20090819
LR  - 20211020
IS  - 1098-2396 (Electronic)
IS  - 0887-4476 (Print)
IS  - 0887-4476 (Linking)
VI  - 63
IP  - 8
DP  - 2009 Aug
TI  - Phenotypic characterization of mice heterozygous for a null mutation of glutamate 
      carboxypeptidase II.
PG  - 625-35
LID - 10.1002/syn.20649 [doi]
AB  - Glutamate is the major excitatory neurotransmitter in the mammalian central 
      nervous system. Disturbed glutamate signaling resulting in hypofunction of 
      N-methyl-D-aspartate receptors (NMDAR) has been implicated in the pathophysiology 
      of schizophrenia. Glutamate Carboxypeptidase II (GCP II) hydrolyzes 
      N-acetyl-alpha L-aspartyl-L-glutamate (NAAG) into glutamate and 
      N-acetyl-aspartate. NAAG is a neuropeptide that is an NMDAR antagonist as well as 
      an agonist for the metabotropic glutamate receptor-3 (mGluR3), which inhibits 
      glutamate release. The aggregate effect of NAAG is thus to attenuate NMDAR 
      activation. To manipulate the expression of GCP II, LoxP sites were inserted 
      flanking exons 1 and 2, which were excised by crossing with a Cre-expressing 
      mouse. The mice heterozygous for this deletion showed a 50% reduction in the 
      expression level of protein and functional activity of GCP II in brain samples. 
      Heterozygous mutant crosses did not yield any homozygous null animals at birth or 
      as embryos (N > 200 live births and fetuses). These data are consistent with the 
      previous report that GCP II homozygous mutant mice generated by removing exons 9 
      and 10 of GCP II gene were embryonically lethal and confirm our hypothesis that 
      GCP II plays an essential role early in embryonic development. Heterozygous mice, 
      however, developed normally to adulthood and exhibited increased locomotor 
      activity, reduced social interaction, and a subtle cognitive deficit in working 
      memory.
FAU - Han, Liqun
AU  - Han L
AD  - Department of Psychiatry, Laboratory of Molecular and Psychiatric Neuroscience, 
      Harvard Medical School and McLean Hospital, Belmont, Massachusetts 02478, USA.
FAU - Picker, Jonathan D
AU  - Picker JD
FAU - Schaevitz, Laura R
AU  - Schaevitz LR
FAU - Tsai, Guochuan
AU  - Tsai G
FAU - Feng, Jiamin
AU  - Feng J
FAU - Jiang, Zhichun
AU  - Jiang Z
FAU - Chu, Hillary C
AU  - Chu HC
FAU - Basu, Alo C
AU  - Basu AC
FAU - Berger-Sweeney, Joanne
AU  - Berger-Sweeney J
FAU - Coyle, Joseph T
AU  - Coyle JT
LA  - eng
GR  - R01 MH051290/MH/NIMH NIH HHS/United States
GR  - P50 MH060450-09/MH/NIMH NIH HHS/United States
GR  - P50 MH060450-0.9/MH/NIMH NIH HHS/United States
GR  - P50 MH060450/MH/NIMH NIH HHS/United States
GR  - R01 MH051290-12/MH/NIMH NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PL  - United States
TA  - Synapse
JT  - Synapse (New York, N.Y.)
JID - 8806914
RN  - 0 (Receptors, Metabotropic Glutamate)
RN  - 0 (metabotropic glutamate receptor 3)
RN  - EC 3.4.17.21 (Glutamate Carboxypeptidase II)
RN  - EC 3.4.17.21 (Glutamate carboxypeptidase III, mouse)
SB  - IM
MH  - Acoustic Stimulation/methods
MH  - Animals
MH  - Behavior, Animal/physiology
MH  - Exons/genetics
MH  - Gene Expression/genetics
MH  - Glutamate Carboxypeptidase II/*deficiency/genetics/metabolism
MH  - *Heterozygote
MH  - Interpersonal Relations
MH  - Memory/physiology
MH  - Mice
MH  - Mice, Knockout
MH  - Motor Activity/genetics
MH  - Mutation/*genetics
MH  - *Phenotype
MH  - Receptors, Metabotropic Glutamate/genetics/metabolism
MH  - Sensory Gating/genetics
MH  - Space Perception/physiology
PMC - PMC2749286
MID - NIHMS133093
EDAT- 2009/04/07 09:00
MHDA- 2009/08/20 09:00
PMCR- 2010/08/01
CRDT- 2009/04/07 09:00
PHST- 2009/04/07 09:00 [entrez]
PHST- 2009/04/07 09:00 [pubmed]
PHST- 2009/08/20 09:00 [medline]
PHST- 2010/08/01 00:00 [pmc-release]
AID - 10.1002/syn.20649 [doi]
PST - ppublish
SO  - Synapse. 2009 Aug;63(8):625-35. doi: 10.1002/syn.20649.