Rob Lipinski1, Chihwa Song2,
Jerry Gipp3, Wade Bushman3, Ian Rowland4
1Bowles Center for Alcohol Research,
University of North Carolina, Chapel Hill, NC, United States; 2Medical
Physics, University of Wisconsin, Madison, WI, United States; 3Urology
Department, University of Wisconsin, Madison, WI, United States; 4Department
of Radiology, University of Wisconsin, Madison, WI, United States
In
utero Hedgehog (Hh) signaling antagonist exposure causes a spectrum of birth
defects including holoprosencephaly (HPE) and cleft lip and palate
(CLP). High resolution MRI and
standard histological methodologies were used to characterize the CNS
phenotype of GD16.5 mouse fetuses exposed to Hh antagonists. HPE fetuses exhibited incompletely
separated cerebral hemispheres and complete pituitary and olfactory bulb
agenesis. Those with CLP exhibited
olfactory bulb hypoplasia and anterior pituitary aplasia. These results demonstrate phenotypic
fidelity of the mouse model to known clinical phenotypes and highlight subtle
CNS abnormalities as are expected to occur in a subset of clinical CLP
populations.
Keywords