Homozygous mutant mice have a perinatal lethal phenotype. They fail to feed or vocalize at birth, and typically die within 48 hours. No protein is detected by immunoblot analysis in tissues (liver, brain, spinal cord, mouse embryonic fibroblasts (MEFs)) from homozygous mutant animals. Microscopic and ultrastructural examination of central nervous system neurons from embryonic day 18 homozygous embryos reveals abnormalities including dysmorphic ventral horn neuron nuclei, vesicles in the neuronal nuclear envelope and enlarged endoplasmic reticulum. Neurons within homozygotes appear normal when migrating, but develop nuclear membrane abnormalities upon maturation.
In contrast to homozygous mutant mice, heterozygotes are viable, fertile, normal in size, and do not manifest any gross physical or behavioral abnormalities. Torsin A (TOR1A) protein levels in heterozygous mice are approximately 50% of wildtype levels. This mutant mouse strain may be useful in studies of torsion dystonia 1 and neurodevelopment.
