TY - JOUR
T1 - Dorsoventral patterning in oesophageal atresia with tracheo-oesophageal fistula
T2 - Evidence from a new mouse model
AU - Ioannides, Adonis S.
AU - Chaudhry, Bill
AU - Henderson, Deborah J.
AU - Spitz, Lewis
AU - Copp, Andrew J.
PY - 2002
Y1 - 2002
N2 - Background/Purpose: The well-established Adriamycin rat model of oesophageal atresia (OA) and tracheo-oesophageal fistula (TOF) complements recently described mouse genetic models in which loss of function mutations in foregut patterning genes, such as Nkx2.1 (Ttf 1), lead to OA/TOF. The authors aimed to integrate the 2 systems by adapting the Adriamycin model to the mouse to study molecular aspects of tracheo-oesophageal development. Methods: Pregnant CBA/Ca mice were injected intraperitoneally with 4 mg/kg of Adriamycin on embryonic days 7.5 and 8.5. Embryos and fetuses of various gestational ages were subjected to morphologic or histologic examination. Sections were stained with H & E or processed for immunohistochemistry using an antibody specific for Nkx2.1. Results: Tracheo-oesophageal malformations were observed in 47% of Adriamycin-treated embryos. Early foregut development was similar in Adriamycin-exposed and control embryos but, by E11.5, many treated embryos had an undivided oesophago-trachea, which gave rise to the lung buds and a fistula to the stomach. The fistula originated from the dorsal aspect of the undivided tube and was negative for Nkx2.1, or showed only transient Nkx2.1 expression, compared to the strongly positive bronchi ventrally. Conclusions: The Adriamycin model of OA is adaptable to the mouse. In the absence of tracheo-oesophageal separation, the dorsal fistula retains its nonrespiratory commitment suggesting that dorsoventral patterning of foregut development is undisturbed by Adriamycin exposure.
AB - Background/Purpose: The well-established Adriamycin rat model of oesophageal atresia (OA) and tracheo-oesophageal fistula (TOF) complements recently described mouse genetic models in which loss of function mutations in foregut patterning genes, such as Nkx2.1 (Ttf 1), lead to OA/TOF. The authors aimed to integrate the 2 systems by adapting the Adriamycin model to the mouse to study molecular aspects of tracheo-oesophageal development. Methods: Pregnant CBA/Ca mice were injected intraperitoneally with 4 mg/kg of Adriamycin on embryonic days 7.5 and 8.5. Embryos and fetuses of various gestational ages were subjected to morphologic or histologic examination. Sections were stained with H & E or processed for immunohistochemistry using an antibody specific for Nkx2.1. Results: Tracheo-oesophageal malformations were observed in 47% of Adriamycin-treated embryos. Early foregut development was similar in Adriamycin-exposed and control embryos but, by E11.5, many treated embryos had an undivided oesophago-trachea, which gave rise to the lung buds and a fistula to the stomach. The fistula originated from the dorsal aspect of the undivided tube and was negative for Nkx2.1, or showed only transient Nkx2.1 expression, compared to the strongly positive bronchi ventrally. Conclusions: The Adriamycin model of OA is adaptable to the mouse. In the absence of tracheo-oesophageal separation, the dorsal fistula retains its nonrespiratory commitment suggesting that dorsoventral patterning of foregut development is undisturbed by Adriamycin exposure.
KW - Adriamycin
KW - Embryology
KW - Gut development
KW - Malformation
KW - Mouse
KW - Nkx2.1 gene expression
KW - Oesophageal atresia
KW - Tracheo-oesophageal fistula
UR - http://www.scopus.com/inward/record.url?scp=0036151989&partnerID=8YFLogxK
U2 - 10.1053/jpsu.2002.30252
DO - 10.1053/jpsu.2002.30252
M3 - Article
C2 - 11819196
AN - SCOPUS:0036151989
SN - 0022-3468
VL - 37
SP - 185
EP - 191
JO - Journal of Pediatric Surgery
JF - Journal of Pediatric Surgery
IS - 2
ER -