The curly tail mouse model of human neural tube defects demonstrates normal spinal cord differentiation at the level of the meningomyelocele: implications for fetal surgery

The paralysis associated with lumbosacral meningomyelocele has been attribu ted both to myelodysplasia and to degeneration of the exposed neural tissue . Surgically created dysraphism shows that exposure of an intact spinal cor d in a genetically normal animal results in degeneration of the normal nerv ous tissue and subsequent paralysis. Our objective was to study neuronal di fferentiation in the curly tail mouse mutant model, which develops lumbosac ral meningomyelocele naturally and is a phenocopy of nonsyndromic human neu ral tube defects. Prenatal repair of meningomyelocele assumes that the norm al neuronal differentiation program occurs despite failure of neurulation. Here we demonstrate that this most suitable animal model has normal differe ntiation of neuronal structures at the level of the meningomyelocele. TuJ1, an antibody to neuronal specific class III beta -tubulin, an early marker of neuronal differentiation, was used to stain paraffin-embedded sections o f curly tail mouse embryo meningomyelocele. Embryos were examined at embryo nic day 13.5 (E13.5). The inbred mouse strain, C57BL6/J, which is genetical ly similar to the curly tail mouse, was used as a control in these studies. We show that early neuronal differentiation appears intact within the meni ngomyelocele. TuJ1 stains structures within the open neural tube. Motor neu rons are present in the ventral horn and ventral roots. Dorsal root ganglia are present and of similar size to controls. The staining pattern is simil ar to that seen in the C57BL/6J control mouse, although dorsal structures a re laterally displaced in the curly tail meningomyelocele. Based on this mo del, fetal surgery to repair human meningomyelocele may preserve neurologic al function in those cases where there is not an inherent genetic defect of the neural tissue.