Neural tube defects and neuroepithelial cell death in Tulp3 knockout mice

The tubby-like protein 3 (Tulp3) gene has been identified as a member of a small novel gene family which is primarily neuronally expressed. Mutations in two of the family members, tub and tulp1, have been shown to cause neuro sensory disorders, To determine the in vivo function of Tulp3, we have gene rated a germline mutation in the mouse Tulp3 gene by homologous recombinati on. Embryos homozygous for the Tulp3 mutant allele exhibit failure of neura l tube closure, and die by embryonic day 14.5, Failure of cranial neural tu be closure coincided with increased neuroepithelial apoptosis specifically in the hindbrain and the caudal neural tube, In addition, the number of bet a III-tubulin positive cells is significantly decreased in the hindbrain of Tulp3(-/-) embryos. These results suggest that disruption of the Tulp3 gen e affects the development of a neuronal cell population. interestingly, som e Tulp3 heterozygotes also manifest embryonic lethality with neuroepithelia l cell death. Our results demonstrate that the Tulp3 gene is essential for embryonic development in mice.