Tethering of the spinal cord in mouse fetuses and neonates with spina bifida.

OBJECT: Tethering of the spinal cord is a well-known complication in humans with spina bifida aperta or occulta. Its pathogenesis consists of a pathological fixation of the spinal cord resulting in traction on the neural tissue which, in turn, leads to ischemia and progressive neurological deterioration. Although well established in humans, this phenomenon has not been described in animal models of spina bifida. METHODS: A fetal mouse model with naturally occurring, genetically determined spina bifida was produced by generating double mutants between the curly tail and loop-tail mutant strains. Microdissection, labeling with 1,1'-dioctadecyl-3,3,3,',3'-tetramethylindocarbocyanine perchlorate, immunohistochemistry for neurofilaments, H & E staining of histological sections, and whole-mount skeletal preparations were performed and comparisons made among mutant and normal fetuses. Normal fetuses exhibited the onset of progressive physiological ascent of the spinal cord from embryonic Day 15.5. Spinal cord ascent resulted, by embryonic Day 18.5, in spinal nerve roots that pass caudolaterally from the spinal cord toward the periphery. In contrast, fetuses with spina bifida exhibited spinal cord tethering that resulted, at embryonic Day 18.5, in nerve roots that run in a craniolateral direction from the spinal cord. The region of closed spinal cord immediately cranial to the spina bifida lesion exhibited marked narrowing, late in gestation, suggesting that a potentially damaging stretch force is applied to the spinal cord by the tethered spina bifida lesion. CONCLUSIONS: This mouse model provides an opportunity to study the onset and early sequelae of spinal cord tethering in spina bifida.