Tor1aΔE mice contain a pathogenic glutamic acid residue deletion in exon 5 of the torsin family 1, member A (torsin A) (Tor1a) gene, resulting in the ΔE knockin. TOR1A is an ATPases Associated with diverse Activities (AAA+) protein residing in the lumen of the ER/nuclear envelope (ER/NE) space. The in-frame ΔE deletion in TOR1A has been shown to cause the autosomal dominant disorder, DYT1 dystonia, which is characterized by abnormal, involuntary twisting movements and muscle contractions due to selective dysfunction of CNS motor circuits. Mice that are homozygous for this allele die within the first day of life due to failure to feed. Heterozygous Tor1aΔE/+ mice are viable and do not display abnormal movements, nor any neuropathological abnormalities when analyzed using standard histopathological methods.
Detailed morphometric studies suggest that medium spiny striatal neurons show fewer and thinner dendrites, and electron microscopy indicates a reduction in the ration of ado-spinous to axo-dendritic inputs to striatum.
This line can be used in conjunction with mice carrying a floxed Tor1a allele (Stock No. 025832) and B6.Cg-Tg(Nes-cre)1Kln/J mice (Stock No. 003771) to generate the first viable model of primary dystonia with overt twisting movements similar to those seen in the human disease; these animals also exhibit selective areas of neurodegeneration in discrete sensorimotor structures. To generate such nestin selective knock-in mice ("N-SKI"), Stock Nos. 025832 and 003771 are first intercrossed to generate animals with one floxed Tor1a allele and the nestin-Cre transgene. These animals are subsequently crossed to this line carrying the ΔE allele (Stock No. 25637) to yield N-SKI Tor1aflox/ΔE Cre+ animals.
