Ectopic expression of class I histocompatibility D(d) proteins during mouse development results in neural tube defects

Previous studies have shown that the overexpression of histocompatibility class I proteins in somatic tissues results in cell dysfunction through non-immune mechanisms. In addition, ubiquitous overexpression of class I D(d) proteins during early development leads to prenatal lethality. Here, we describe transgenic mice in which ectopic class I D(d) expression results in neural tube defects. In these mice, the D(d) gene is regulated by the mouse α-fetoprotein enhancer III region. The defects are seen in two independent transgenic lines and the defect is influenced by the absence of the class I-associated subunit, β2-microglobulin. This demonstrates a link between ectopic D(d) expression and neural tube defects and suggests that elevated class I expression during early development may be a risk factor for these abnormalities.