Curly tail: a 50-year history of the mouse spina bifida model

This paper reviews 50 years of progress towards understanding the aetiology and pathogenesis of neural tube defects (NTD) in the curl? rail (ct) mutan t mouse. More than 45 papers have been published on various aspects of curl y tail with the result that it is now the best understood mouse model of NT D pathogenesis. The failure of closure of the spinal neural tube, which lea ds to spina bifida in this mouse, has been traced back to a tissue-specific defect of cell proliferation in the tail bud of the E9.5 embryo. This cell proliferation defect results in a growth imbalance in the caudal region th at generates ventral curvature of the body axis. Neurulation movements are opposed. leading to delayed neuropore closure and spina bifida, or tail def ects. It is interesting to reflect that these advances have been achieved i n the absence of information on the nature of the ct gene product, which re mains unidentified. In addition to the principal ct gene, which maps to dis tal Chromosome 4, the curly tail phenotype is influenced by several modifie r genes and by environmental factors. NTD in curly tail are resistant to fo lic acid, as is thought to be the case in 30% of human NTD. whereas they ca n be prevented by myo-inositol. These and other features of NTD in this sys tem bear striking similarities to the situation in humans, making curly rai l a model for understanding a sub-type folic acid-resistant human NTD.