The Nuclear Factor I (NFI) multi-gene family encodes site-specific
transcription factors essential for the development of a number of
organ systems. We showed previously that Nfia-deficient mice exhibit
agenesis of the corpus callosum and other forebrain defects, Nfib-
deficient mice have defects in lung maturation and show callosal
agenesis and forebrain defects resembling those seen in Nfia-
deficient animals, while Nfic-deficient mice have defects in tooth
root formation.
Recently the Nfix gene has been disrupted and these studies indicated
that there were largely uncharacterized defects in brain and skeletal
development in Nfix-deficient mice.
Results: Here we show that disruption of Nfix by Cre-recombinase
mediated excision of the 2nd exon results in defects in brain
development that differ from those seen in Nfia and Nfib KO mice. In
particular, complete callosal agenesis is not seen in Nfix-/- mice
but rather there appears to be an overabundance of aberrant Pax6- and
doublecortin-
mice, increased brain weight, expansion of the cingulate cortex and
entire brain along the dorsal ventral axis, and aberrant formation of
the hippocampus.
On standard lab chow Nfix-/- animals show a decreased growth rate
from ~P8 to P14, lose weight from ~P14 to P22 and die at ~P22. If
their food is supplemented with a soft dough chow from P10, Nfix-/-
animals show a lag in weight gain from P8 to P20 but then increase
their growth rate.
A fraction of the animals survive to adulthood and are fertile. The
weight loss correlates with delayed eye and ear canal opening and
suggests a delay in the development of several epithelial structures
in Nfix-/- animals.
Conclusions: These data show that Nfix is essential for normal brain
development and may be required for neural stem cell homeostasis. The
delays seen in eye and ear opening, and the brain morphology defects
appear independent of the nutritional deprivation, as rescue of
perinatal lethality with soft dough does not eliminate these defects.
Author: Christine E Campbell, Michael Piper, Celine Plachez, Yu-Ting
Yeh, Joan S Baizer, Jason M Osinski, E. David Litwack, Linda J
Richards and Richard M Gronostajski
Credits/Source: BMC Developmental Biology 2008, 8:52
Published on: 2008-05-13
http://7thspace.
essential_for_
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StemCells subscribers may also be interested in these sites:
Children's Neurobiological Solutions
http://www.CNSfoundation.org/
Cord Blood Registry
http://www.CordBlood.com/at.cgi?a=150123
The CNS Healing Group
http://groups.yahoo.com/group/CNS_Healing
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