A mouse model for neural tube defects: the curtailed (Tc) mutation produces spina bifida occulta in Tc/+ animals and spina bifida with meningomyelocele in Tc/t.
Curtailed (Tc), a dominant mutation on mouse chromosome 17, causes a tailless phenotype and occasional hindlimb paralysis in heterozygotes. Histologically, Tc/+ embryos show a variety of abnormalities including budding and ventral duplication of the developing spinal cord, duplication and intermittent absence of the notochord, and partial or complete absence of bony vertebrae, all posterior to midliver level. When Tc is heterozygous with t-haplotypes that contain the "tail interaction factor," tct, the phenotype is more severe, and a dorsal blood blister exists in the lumbosacral area. Our microscopic observations reveal that Tc/tw5 mice have a lumbosacral spina bifida with meningomyelocele. This results from the absence of bony vertebrae, extensive thinning of the dermis dorsally, and the rupturing of the previously closed neural tube, probably by increased cerebrospinal fluid (CSF) pressure on the necrotic, attenuated roof plate. Thinning of the roof plate, which facilitates the rupturing of the spinal cord, is not observed in Tc/+, which suggests that this phenomenon is associated with the interaction of Tc with the t-allele. Later in the development of Tc/tw5 embryos, adjacent blood vessels are ruptured, resulting in hemorrhage into the CSF space to give the external appearance of a blood blister. Tc/+ mice also show an absence of bony vertebrae dorsally in the lumbosacral region, but they lack the dorsal blood blister, and the dermal layer overlying the bony defect retains its normal thickness; these observations describe a spina bifida occulta.
Park
C H
CH
University of Texas, Austin 78712-1064.
Pruitt
J H
JH
Bennett
D
D
D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D005838:Genotype; D005865:Gestational Age; D008591:Meningomyelocele / Q000196:embryology / Q000235:genetics* / Q000473:pathology; D051379:Mice; D008818:Mice, Neurologic Mutants; D011247:Pregnancy; D016136:Spina Bifida Occulta / Q000196:embryology / Q000235:genetics* / Q000473:pathology