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@ARTICLE{Feldner:125248,
author = {A. Feldner$^*$ and M. G. Adam$^*$ and F. Tetzlaff$^*$ and
I. Moll$^*$ and D. Komljenovic$^*$ and F. Sahm$^*$ and T.
Bäuerle$^*$ and H. Ishikawa and H. Schroten and T. Korff
and I. Hofmann$^*$ and H. Wolburg and A. von Deimling$^*$
and A. Fischer$^*$},
title = {{L}oss of {M}pdz impairs ependymal cell integrity leading
to perinatal-onset hydrocephalus in mice.},
journal = {EMBO molecular medicine},
volume = {9},
number = {7},
issn = {1757-4684},
address = {Weinheim},
publisher = {Wiley-VCH},
reportid = {DKFZ-2017-01400},
pages = {890 - 905},
year = {2017},
abstract = {Hydrocephalus is a common congenital anomaly. LCAM1 and
MPDZ (MUPP1) are the only known human gene loci associated
with non-syndromic hydrocephalus. To investigate functions
of the tight junction-associated protein Mpdz, we generated
mouse models. Global Mpdz gene deletion or conditional
inactivation in Nestin-positive cells led to formation of
supratentorial hydrocephalus in the early postnatal period.
Blood vessels, epithelial cells of the choroid plexus, and
cilia on ependymal cells, which line the ventricular system,
remained morphologically intact in Mpdz-deficient brains.
However, flow of cerebrospinal fluid through the cerebral
aqueduct was blocked from postnatal day 3 onward. Silencing
of Mpdz expression in cultured epithelial cells impaired
barrier integrity, and loss of Mpdz in astrocytes increased
RhoA activity. In Mpdz-deficient mice, ependymal cells had
morphologically normal tight junctions, but expression of
the interacting planar cell polarity protein Pals1 was
diminished and barrier integrity got progressively lost.
Ependymal denudation was accompanied by reactive
astrogliosis leading to aqueductal stenosis. This work
provides a relevant hydrocephalus mouse model and
demonstrates that Mpdz is essential to maintain integrity of
the ependyma.},
cin = {A270 / E020 / G380 / A190 / L101},
ddc = {610},
cid = {I:(DE-He78)A270-20160331 / I:(DE-He78)E020-20160331 /
I:(DE-He78)G380-20160331 / I:(DE-He78)A190-20160331 /
I:(DE-He78)L101-20160331},
pnm = {311 - Signalling pathways, cell and tumor biology
(POF3-311)},
pid = {G:(DE-HGF)POF3-311},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:28500065},
pmc = {pmc:PMC5494508},
doi = {10.15252/emmm.201606430},
url = {https://inrepo02.dkfz.de/record/125248},
}