Neural tube defects (NTDs), including anencephaly and spina bifida,
are the second most common birth defect in humans, with a frequency of
approximately 1/1000 births. NTDs are caused by the failure of the
neural tube to close during early development of the brain and spinal
cord. Closure failure in the part of the neural tube that forms the
brain results in anencephaly (called exencephaly in mice). The brain
forms completely abnormally and the cranium is absent, resulting in
death at birth.
We are studying the gene Cecr2, which when mutated causes exencephaly in mice (Banting et al, 2005). We study two different mutations of Cecr2, a deletion mutation causing exencephaly in 100% of mutants, and a gene trap mutation causing exencephaly in ~54% of mutants. In the latter strain, the surviving mutants show reduced fertility in both males and females (Thompson et al, 2012). The defect also depends on the mouse strain: the gene trap mutation on a BALB/c mouse strain shows exencepahly in ~54% of embryos, but this same mutation on the FVB/N mouse strain shows relatively normal brain development in all embryos (Banting et al, 2005, Dawe et al, 2011). We have mapped to mouse chromosome 19 genes that modify Cecr2-induced exencephaly, partially leading to the strain difference in susceptibility (Davidson et al, 2007, Kooistra et al, 2012). Exploration of Cecr2 and it’s major modifiers will add to our understanding of both neural tube defects and the mechanisms of normal neurulation.