PMID- 23213205
OWN - NLM
STAT- MEDLINE
DCOM- 20130228
LR  - 20211021
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Print)
IS  - 0027-8424 (Linking)
VI  - 109
IP  - 51
DP  - 2012 Dec 18
TI  - Reduced axonal localization of a Caps2 splice variant impairs axonal release of 
      BDNF and causes autistic-like behavior in mice.
PG  - 21104-9
LID - 10.1073/pnas.1210055109 [doi]
AB  - Ca(2)(+)-dependent activator protein for secretion 2 (CAPS2 or CADPS2) potently 
      promotes the release of brain-derived neurotrophic factor (BDNF). A rare splicing 
      form of CAPS2 with deletion of exon3 (dex3) was identified to be overrepresented 
      in some patients with autism. Here, we generated Caps2-dex3 mice and verified a 
      severe impairment in axonal Caps2-dex3 localization, contributing to a reduction 
      in BDNF release from axons. In addition, circuit connectivity, measured by spine 
      and interneuron density, was diminished globally. The collective effect of 
      reduced axonal BDNF release during development was a striking and selective 
      repertoire of deficits in social- and anxiety-related behaviors. Together, these 
      findings represent a unique mouse model of a molecular mechanism linking 
      BDNF-mediated coordination of brain development to autism-related behaviors and 
      patient genotype.
FAU - Sadakata, Tetsushi
AU  - Sadakata T
AD  - Advanced Scientific Research Leaders Development Unit, Gunma University, 
      Maebashi, Gunma 371-8511, Japan. sadakata-1024@umin.ac.jp
FAU - Shinoda, Yo
AU  - Shinoda Y
FAU - Oka, Megumi
AU  - Oka M
FAU - Sekine, Yukiko
AU  - Sekine Y
FAU - Sato, Yumi
AU  - Sato Y
FAU - Saruta, Chihiro
AU  - Saruta C
FAU - Miwa, Hideki
AU  - Miwa H
FAU - Tanaka, Mika
AU  - Tanaka M
FAU - Itohara, Shigeyoshi
AU  - Itohara S
FAU - Furuichi, Teiichi
AU  - Furuichi T
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20121203
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (CAPS2 protein, mouse)
RN  - 0 (Calcium-Binding Proteins)
RN  - 0 (Glial Cell Line-Derived Neurotrophic Factor)
RN  - 0 (Nerve Tissue Proteins)
SB  - IM
MH  - Alternative Splicing
MH  - Animals
MH  - Anxiety
MH  - Autistic Disorder/genetics/*metabolism
MH  - Axons/*metabolism
MH  - Brain/metabolism
MH  - Brain Mapping/methods
MH  - Brain-Derived Neurotrophic Factor/metabolism
MH  - Calcium-Binding Proteins/*genetics/*physiology
MH  - Crosses, Genetic
MH  - Exocytosis
MH  - Exons
MH  - *Gene Expression Regulation
MH  - Glial Cell Line-Derived Neurotrophic Factor/metabolism
MH  - Mice
MH  - Models, Genetic
MH  - Models, Neurological
MH  - Nerve Tissue Proteins/*genetics/*physiology
MH  - Neurons/metabolism
MH  - Risk Factors
MH  - Social Behavior
PMC - PMC3529019
COIS- The authors declare no conflict of interest.
EDAT- 2012/12/06 06:00
MHDA- 2013/03/01 06:00
PMCR- 2013/06/18
CRDT- 2012/12/06 06:00
PHST- 2012/12/06 06:00 [entrez]
PHST- 2012/12/06 06:00 [pubmed]
PHST- 2013/03/01 06:00 [medline]
PHST- 2013/06/18 00:00 [pmc-release]
AID - 1210055109 [pii]
AID - 201210055 [pii]
AID - 10.1073/pnas.1210055109 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 2012 Dec 18;109(51):21104-9. doi: 
      10.1073/pnas.1210055109. Epub 2012 Dec 3.