PMID- 24336072
OWN - NLM
STAT- MEDLINE
DCOM- 20140423
LR  - 20230216
IS  - 1530-0307 (Electronic)
IS  - 0023-6837 (Linking)
VI  - 94
IP  - 3
DP  - 2014 Mar
TI  - Truncated Cables1 causes agenesis of the corpus callosum in mice.
PG  - 321-30
LID - 10.1038/labinvest.2013.146 [doi]
AB  - Agenesis of the corpus callosum (ACC) is a congenital abnormality of the brain 
      structure. More than 60 genes are known to be involved in corpus callosum 
      development. However, the molecular mechanisms underlying ACC are not fully 
      understood. Previously, we produced a novel transgenic mouse strain, TAS, 
      carrying genes of the tetracycline-inducible expression system that are not 
      involved in brain development, and inherited ACC was observed in the brains of 
      all homozygous TAS mice. Although ACC was probably induced by transgene insertion 
      mutation, the causative gene and the molecular mechanism of its pathogenesis 
      remain unclear. Here, we first performed interphase three-color fluorescence in 
      situ hybridization (FISH) analysis to determine the genomic insertion site. 
      Transgenes were inserted into chromosome 18  approximately 12.0 Mb from the centromere. Gene 
      expression analysis and genomic PCR walking showed that the genomic region 
      containing exon 4 of Cables1 was deleted by transgene insertion and the other 
      exons of Cables1 were intact. The mutant allele was designated as Cables1(TAS). 
      Interestingly, Cables1(TAS) mRNA consisted of exons 1-3 of Cables1 and part of 
      the transgene that encoded a novel truncated Cables1 protein. Homozygous TAS mice 
      exhibited mRNA expression of Cables1(TAS) in the fetal cerebrum, but not that of 
      wild-type Cables1. To investigate whether a dominant negative effect of 
      Cables1(TAS) or complete loss of function of Cables1 gives rise to ACC, we 
      produced Cables1-null mutant mice. ACC was not observed in Cables1-null mutant 
      mice, suggesting that a dominant negative effect of Cables1(TAS) impairs callosal 
      formation. Moreover, ACC frequency in Cables1(+/TAS) mice was significantly lower 
      than that in Cables1(-/TAS) mice, indicating that wild-type Cables1 interfered 
      with the dominant negative effect of Cables1(TAS). This study indicated that 
      truncated Cables1 causes ACC and wild-type Cables1 contributes to callosal 
      formation.
FAU - Mizuno, Seiya
AU  - Mizuno S
AD  - Laboratory Animal Resource Center, University of Tsukuba, Tsukuba, Japan.
FAU - Tra, Dinh T H
AU  - Tra DT
AD  - Laboratory Animal Resource Center, University of Tsukuba, Tsukuba, Japan.
FAU - Mizobuchi, Atsushi
AU  - Mizobuchi A
AD  - Laboratory Animal Resource Center, University of Tsukuba, Tsukuba, Japan.
FAU - Iseki, Hiroyoshi
AU  - Iseki H
AD  - 1] Laboratory Animal Resource Center, University of Tsukuba, Tsukuba, Japan [2] 
      Project Research Division, Research Center for Genomic Medicine, Saitama Medical 
      University, Saitama, Japan.
FAU - Mizuno-Iijima, Saori
AU  - Mizuno-Iijima S
AD  - Laboratory Animal Resource Center, University of Tsukuba, Tsukuba, Japan.
FAU - Kim, Jun-Dal
AU  - Kim JD
AD  - Life Science Center, Tsukuba Advanced Research Alliance, Graduate School of Life 
      and Environmental Sciences, University of Tsukuba, Tsukuba, Japan.
FAU - Ishida, Junji
AU  - Ishida J
AD  - Life Science Center, Tsukuba Advanced Research Alliance, Graduate School of Life 
      and Environmental Sciences, University of Tsukuba, Tsukuba, Japan.
FAU - Matsuda, Yoichi
AU  - Matsuda Y
AD  - Laboratory of Animal Genetics, Graduate School of Bioagricultural Sciences, 
      Nagoya University, Nagoya, Japan.
FAU - Kunita, Satoshi
AU  - Kunita S
AD  - Center for Experimental Medicine, Jichi Medical University, Shimotsuke, Japan.
FAU - Fukamizu, Akiyoshi
AU  - Fukamizu A
AD  - Life Science Center, Tsukuba Advanced Research Alliance, Graduate School of Life 
      and Environmental Sciences, University of Tsukuba, Tsukuba, Japan.
FAU - Sugiyama, Fumihiro
AU  - Sugiyama F
AD  - Laboratory Animal Resource Center, University of Tsukuba, Tsukuba, Japan.
FAU - Yagami, Ken-ichi
AU  - Yagami K
AD  - Laboratory Animal Resource Center, University of Tsukuba, Tsukuba, Japan.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20131216
PL  - United States
TA  - Lab Invest
JT  - Laboratory investigation; a journal of technical methods and pathology
JID - 0376617
RN  - 0 (Cables1 protein, mouse)
RN  - 0 (Carrier Proteins)
RN  - 0 (Cyclins)
RN  - 0 (Phosphoproteins)
RN  - 0 (RNA, Messenger)
SB  - IM
MH  - Agenesis of Corpus Callosum/*genetics/metabolism/pathology
MH  - Animals
MH  - Carrier Proteins/*genetics
MH  - Cyclins/*deficiency/*genetics
MH  - Exons
MH  - Genetic Association Studies
MH  - Homozygote
MH  - In Situ Hybridization, Fluorescence
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Inbred C57BL
MH  - Mice, Inbred ICR
MH  - Mice, Knockout
MH  - Mice, Transgenic
MH  - Mutagenesis, Insertional
MH  - Phosphoproteins/*deficiency/*genetics
MH  - RNA, Messenger/genetics/metabolism
EDAT- 2013/12/18 06:00
MHDA- 2014/04/24 06:00
CRDT- 2013/12/17 06:00
PHST- 2013/08/27 00:00 [received]
PHST- 2013/11/07 00:00 [revised]
PHST- 2013/11/08 00:00 [accepted]
PHST- 2013/12/17 06:00 [entrez]
PHST- 2013/12/18 06:00 [pubmed]
PHST- 2014/04/24 06:00 [medline]
AID - S0023-6837(22)00841-8 [pii]
AID - 10.1038/labinvest.2013.146 [doi]
PST - ppublish
SO  - Lab Invest. 2014 Mar;94(3):321-30. doi: 10.1038/labinvest.2013.146. Epub 2013 Dec 
      16.