In brain tissue, levels of PAX3 were significantly reduced in both encephalocele and spina bifida subtypes; the expression levels of cleaved caspase 3(17 kD) of encephalocele cases and cleaved caspase 8(47/45 kD) in spina bifida cases were higher than in controls; no difference was found in the expression of p53 or caspase 9 between NTDs and controls.
Crossing the Sp (Splotch) mutation in the Pax3 gene onto the FVB/N background for two generations indicated that this resistant strain also decreases the penetrance of spina bifida.
While further studies continue, possible interpretations include involvement of a regulatory gene(s) for PAX 3 and other genes at the other breakpoints related causally to the spina bifida and mental retardation.