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Genetic dissection of hyperthermia-induced neural tube defects in mice
Yunxia Wang Lundberg1, Michael J Wing, Wanfen Xiong
1Boys Town National Research Hospital, Genetics Department, Omaha, Nebraska 68131, USA. lundbergy@boystown.org
Background:
Maternal hyperthermia has been shown to induce neural tube defects (NTD) in humans and in experimental animal systems. We report the first genetic dissection of maternal hyperthermia-induced NTD in mice.
Methods:
After maternal exposure on E8.5 to 43 degrees C water bath for 10 min, we observed exencephaly frequencies among E15.5-17.5 fetuses from the following crosses and backcrosses, SWV/Fnn(SWV)xSWV, C57BL/6J(C57)xC57, SWVxC57 (F1), F1xSWV and SWVxF1.
Results:
The fetuses with maternal hyperthermia exposure developed exencephaly in a strain-dependent manner and the exencephaly frequencies among the above crosses were 46.2, 14.3, 13.6, 11.3, and 27.0%, respectively, expressed over total live fetuses. The fetal death rates were 47.3, 24.6, 37.1, 4.3, and 35.5%, respectively, expressed over total implants.
Conclusion:
The data demonstrate that a single fetal genetic locus, plus a maternal effect, have likely caused the strain differences in the susceptibility to hyperthermia-induced exencephaly. A maternal effect alone may have caused the higher prenatal mortality rates in the SWVxF1 cross versus the reciprocal cross. Analysis of gender ratios among those affected from these crosses excludes an X- or Y-linked effect in causing the higher numbers of affected females.