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BSP-14
(P)
THE MURINE MODEL OF URINARY TRACT ABNORMALITIES THAT ARE SEEN IN
THE VACTERL ASSOCIATION
Parkash MANDHAN
Hamad Medical Corporation, Department of Paediatric Surgery, Halilton, NEW ZEALAND
PURPOSE
The VACTERL syndrome is a common surgical condition affecting the development of many midaxial organs. We report
here urinary tract abnormalities seen in a murine model of VACTERL association similar to those seen in humans.
MATERIAL AND METHODS
Time-mated pregnant rats received 125 mg/kg of 1% Ethylenethiourea (ETU) (experimental group) or vehicle only
(control). Their fetuses were examined for urinary tract anomalies and concurrent anorectal, vertebral and limb
malformations. Histological sections were prepared to study the morphogenesis of various malformations followed by
gene expression studies.
RESULTS
In ETU-exposed fetuses, individual malformations of urinary tract, anorectum, vertebrae and limbs occurred in 54%,
98%, 42% and 34% respectively. VACTERL syndrome (concurrence of 3 malformations) was observed in 13% fetuses in
experimental group. Gene expression studies showed reduced expression ofShhand downstream target genes in limb
buds, notochord and in cloacal derivatives.
CONCLUSIONS
We conclude that this murine model of VACTERL association will support to further clarify the molecular and
morphogenetic processes that lead to many of the structural congenital abnormalities that are seen in infants born with
the VACTERL association.